Pineal Neurosurgery [1st ed.] 9783030531904, 9783030531911

Citation preview

Pineal Neurosurgery Samer S. Hoz Ali A. Dolachee Hayder R. Salih Zaid S. Aljuboori Wisam D. Selbi Giath Al-Dayri Mohammed Maan Al-Salihi Editors

123

Pineal Neurosurgery

Samer S. Hoz  •  Ali A. Dolachee Hayder R. Salih  •  Zaid S. Aljuboori Wisam D. Selbi  •  Giath Al-Dayri Mohammed Maan Al-Salihi Editors

Pineal Neurosurgery

Editors Samer S. Hoz Neurosurgery Teaching Hospital Baghdad Iraq Hayder R. Salih Neurosurgery Teaching Hospital Baghdad Iraq Wisam D. Selbi South West Deanery Department of Neurosurgery Plymouth UK Mohammed Maan Al-Salihi Ludmillenstift Hospital Department of Neurosurgery & Spine Surgery Meppen Germany

Ali A. Dolachee University of Al-Qadisiyah College of Medicine Department of Surgery Diwaniyah Iraq Zaid S. Aljuboori University of Louisville Department of Neurological Surgery Louisville Kentucky USA Giath Al-Dayri Ludmillenstift Hospital Department of Neurosurgery & Spine Surgery Meppen Germany

ISBN 978-3-030-53190-4    ISBN 978-3-030-53191-1 (eBook) https://doi.org/10.1007/978-3-030-53191-1 © Springer Nature Switzerland AG 2020 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

To my lovely family: Sawsan, Saad, Samher, Arwa, Farah, and Ward Samer S. Hoz To my lovely family which support me in this long way, neurosurgery Ali A. Dolachee My dad Salih, my mom Suaad, my love Rosa, and my angel Ghazal Hayder R. Salih To my family who always supported me and helped me to be the man I am Zaid S. Aljuboori I dedicate my work to my family and mentors for their help, support, and encouragement Wisam D. Selbi To Dr. Nuri Bahjet. A true human being Giath Al-Dayri To Mariam, the girl who believed in me since the very first sight Mohammed Maan Al-Salihi

Foreword 1

Given the rarity of lesions encompassing the pineal region and of real pineal gland tumors, which are seldom encountered in daily neurosurgical practice, a lack of knowledge and understanding of the pineal gland role and of tumors in this area does clearly exist. This book is written mostly by neurosurgeons for neurosurgeons and deals with the topic in a comprehensive way, covering all the aspects of the physiological role and the pathological entities involving the gland and the area. Of particular interest for young neurosurgeons are the chapters on anatomy, treatment and approaches, and the one on surgical training. Surgical approaches are covered in a brief, practical, and easily understandable but complete format. Rules of the thumb for clinical practice are provided too. Apart from this critique, this book is a unique and up-to-date resource for all the members of the Neurosurgical Community, either in training or experts, and we do recommend its presence on the shelves of every neurosurgeon interested in the treatment of brain tumors. Franco Servadei Department of Neurosurgery Humanitas University and Research Hospital Milano, Italy Giovanni Battista Lasio Department of Neurosurgery Humanitas University and Research Hospital Milano, Italy

vii

Foreword 2

The book edited by Hoz et al. neurosurgery of pineal gland is filling some vacant space in neurosurgical literature. Until recently, the pineal gland, its pathologies and treatment options have not been published as comprehensively as in this book. However, the editors included separate chapters on embryology, neuroanatomy, physiology, and neuroimaging. These chapters are making the book particularly interesting since all the aspects are covered and the reader gets the whole picture of the pineal gland. The chapter on physiology is extremely welcome, it clearly shows how important the pineal gland is and how many systems are affected by its hormone—melatonin. Chapters on embryology and neuroanatomy are very interesting to read; the anatomy is very well described and pictured. Chapters 5–7 are the main core of the book for a neurosurgeon. Tumors of the pineal gland, Chap. 5, follows the last WHO classification and clearly describes various treatment modalities, prognosis, and behavior of the pineal gland tumors. Chapter 6, non-tumorous lesions perfectly fills and adds knowledge on particularly quite common pineal cysts and other non-tumorous lesions. Chapter 7, approaches to the pineal region is pure and clean neurosurgery. The approaches are well described and pictured; none is omitted and their value and specific use is well described. Chapter 8, interesting cases is very valuable from the clinical point of view; it depicts the importance of the region clinically. Surgical training, Chap. 9, is a nice and interesting description of a sheep model. Since the surgery in the pineal gland region is not a common endeavor, its value is very high for anyone who is interested in entering this area of neurosurgery. The last chapter, evolutionary retrace of the third eye with very interesting data are available. Chapters 1–7 are presented in a specific, rapid fire form of bullets and succinct data. It is easy to follow and it is very didactic. The educational value of the book is enhanced by multiple-choice short tests at the end of Chaps. 1–7. At the end of the chapters, very comprehensive list of references to each chapter is provided. Such a reference division easily allows the reader to go deeper into any specific area.

ix

x

Foreword 2

In conclusion, the book is well composed, easy to use; it gives all important data on pineal gland. It fills the gap in neurosurgical literature and as such it helps anyone interested to get the important information on any aspect of pineal gland and its pathologies. Vladimír Beneš European Association of Neurosurgical Societies Prague, Czech Republic

Foreword 3

This book on the pineal region is another great effort for Samer and Co. It is refreshing to see how they have covered each part of this topic to make it into a complete all perspective covered book, quite different from the books that one would get at the moment. Wishing them all the best to continue this trend and keep young neurosurgeons in focus. Iype Cherian Asian Congress of Neurological Surgeons Member, WFNS Anatomy Committee Department of Neurosurgery, COMS Bharatpur, Nepal

xi

Foreword 4

In accordance with the ongoing technological advancement in the biomedical field, particularly in the last few years, we have been experiencing a volatile modification in planning and conduction of neurosurgical operations. High-resolution imaging, 3-D modalities, neuronavigation, functional MRI, neuroendoscopy, and neuromonitoring are continually redefining minimal invasiveness and improving the overall surgical outcome. With respect to surgery of the pineal region, extensive case-by-case planning is crucial for maximization of patient outcome, as with, for instance, planning of the surgical approach, and the pre-operative identification of the important structures to avoid damaging intraoperatively, such as the large cerebral veins. Surgery of the pineal gland is particularly challenging, due to the anatomical and physiological nature of it, rendering aspects like tumor localization and size of importance in surgical planning. Frequently, a supracerebellar infratentorial surgical approach is best implemented, and in such cases, we would extensively adopt a semi-sitting position. Another key measure is the extensive release of CSF from the Cisterna Magna to operate with more freedom in the midline just above the cerebellum, with minimal tissue manipulation and optimal exposure of the vessels in the pineal region. Endoscopy in such operations could be utilized as a standalone method, but it might as well be used as a supportive “look around the corner” tool. Whenever possible, I have always favored minimally invasive, fully endoscopic, transventricular access to the pineal region. This requires thorough planning, as it is decisive to obtain ideal trajectories over the lateral ventricles, the foramen of Monroe, and the third ventricle, to minimize collateral damage. Far frontal approach for optimal trajectory, and sufficient burr hole size are therefore essential for optimization of the endoscopic operation. Since the introduction of high definition technique in the neuroendoscopic procedures, and more recently 3D endoscopy, these minimally invasive procedures are being performed to a higher level of patient safety and practicality. In cases of pineal tumors associated with hydrocephalus, we tend to perform third ventriculostomy initially, to be followed by the main operation of the pineal pathology via the same or second trajectory. In such cases, we would incorporate a two burr-hole craniotomy, one far frontal for endoscopic tumor biopsy, resection, or fenestration of a pineal cyst; and another burr hole around the coronary suture for performing the third ventriculostomy. xiii

xiv

Foreword 4

Significant challenges in pineal region operations lie in the preservation and/or minimizing the damage of the large central veins, tectum, thalamus, and brain stem. An important decision to be made in this regard is the extent of resection, which is to be carefully balanced against potential neurological deficits. This also applies to pineal cysts, which are sufficiently operated with extended resection of the main bulk of the cyst, rather than complete removal which is often associated with significant risk of bleeding. Pathologies of the pineal region in general and pineal tumors specifically are not very common. And in our hospital, they are usually incidental findings, emerging from the increased usage of MRI diagnostics with common symptoms such as headache. A large number of pineal cysts are small and asymptomatic, requiring no operation. However, some cysts lead to intermittent occlusive hydrocephalus with aqueductal stenosis. This might not be evident in medical imaging, and therefore quite difficult to diagnose. This requires extensive knowledge and experience to decide whether corresponding surgery is indicated. With regard to the pineal gland, we are lacking a sufficient single-resource overview of its rare pathologies and various management approaches. A book that tackles anatomy, pathology, and management of pineal tumors is innovative and valuable. And in view of the highly complex nature of the corresponding operations, I believe that the challenging task of Dr. Hoz and the co-authors of PINEAL NEUROSURGERY will ultimately succeed in achieving this goal. Sincerely yours Christoph A. Tschan Neurosurgical Department and Spine Center Ludmillenstift Hospital Meppen, Germany

Preface

Rene´ Descartes (1596–1650) who gave the unique description of the pineal gland as being of “the seat of man’s soul.” Since then, many scientists have been exploring the structural composition, physiology, and pathology of this gland. The Neurosurgery of the Pineal Gland is a unique medical book for students and clinicians, especially in the field of neurosciences. It provides a detailed body of information important for the understanding of the biological and clinical aspects of the pineal gland. This book presents clinical information extracted from a large body of literature regarding the pineal gland. It covers key points of the diagnosis, clinical presentation, radiological findings, pathology and treatment of diseases of the pineal gland. This book is designed to start with the basic Embryology of the Pineal Gland, then moving toward discussing its anatomy, physiology, imaging characteristics, pathological conditions, and treatment approaches. This is not intended to provide an in-depth coverage of the pineal gland, rather it is intended to act as a manual for clinicians to be able to quickly review topics regarding different aspects of the pineal gland. We envision that this text will be used by medical students, neurosurgery and neurology residents around the world to learn the basics of the pineal gland, also it serves as a valuable resource to practicing neurosurgeons and neurologists. It is our hope that this book will help to create a solid foundation of basic knowledge of the pineal gland that can be further developed by individual learners. Baghdad, Iraq Diwaniyah, Iraq  Baghdad, Iraq  Louisville, KY  Plymouth, UK  Meppen, Germany  Meppen, Germany 

Samer S. Hoz Ali A. Dolachee Hayder R. Salih Zaid S. Aljuboori Wisam D. Selbi Giath Al-Dayri Mohammed Maan Al-Salihi

xv

Key Features

1. PINEAL NEUROSURGERY is the first book that vastly focuses on neurosurgical aspects of the pineal gland, emerging from the momentous need to fill the gap in the neurosurgical resources map and incorporate meaningful updates regarding all aspects of the pineal gland. Many books were dedicated to the pineal gland over the years, but those were essentially written to fulfill a philosophical, endocrinological, or pathological perquisites. 2. PINEAL NEUROSURGERY is composed of ten chapters, containing concise and up-to-date information that all high yield in any neurosurgical exam which makes the book greatly beneficial for all neurosurgical degree candidates or though seeking refreshment. 3. The book contains diagrams, tables, illustrations, and figures attempting to make it more interesting and easier to memorize by the readers. 4. More than 70 single best answer multiple-choice questions (MCQs), distributed along the chapters, covering important aspects of the pineal gland, from embryology, anatomy, physiology, pathology, and ultimately surgery as well as from evolutionary aspect. The PINEAL NEUROSURGERY is an essential review for residents and surgeons across neurosurgical disciplines and contains most of the critical information required to prepare for the certification exam.

xvii

Acknowledgments

To the founders of neurological surgery in IRAQ: Dr. Saad H. Al-Witry, Dr. Anwer Noori Hafidh, Dr. Tariq Abdul-Wahid, Dr. Sameer H. Aboud, Dr. Rafid Al-Saffar, Dr. Hikmat Sideeq, Dr. A Hadi Al Khalili, Dr. Imad Hashim Ahmad, Dr. Ari Sami H. Nadhim, Dr. Ali K. Alshalchy, Dr. Moneer K. Faraj, DR. Abdulameer Jasim, Dr. Ahmad Adnan Al-Juboury, Dr. Ammar M. Al-Smaysim, Dr. Wamedh E. Matti. The editors also have a lot of appreciation and gratitude to the supporting seniors and colleagues in the Neurosurgery Teaching Hospital in Baghdad, Iraq, especially: Dr. Wisam Hussein, Dr. Saif Saood, Dr. Ahmed Hamed Ibrahim, Dr. Hussein J Kadhum, Dr. Abdulqadder nabil, Dr. Arjan A Najim, Dr. Mukarram Nooraldeen Musarhad, Dr. Gulshan Talat Muhammed, Dr. Mustafa M.  Altaweel, Dr. Alaa H. Arakwazi, Dr. Haitham Ahmed Obaid, Dr. Mohammed Burhan, Dr. Yaqthan Al-­ Azawi, Dr. Ahmad Amman, Dr. Jasem Mohammed, Dr. Ahmed Radhi Obaid, Dr. Sadik Fadhel, Dr. Haider Tawfeeq, Dr. Kadhum Al-Khozaai, Dr. Waleed Al-Hayali, Dr. Raad Sajed, Dr. Basim Nema, Dr. Riyadh Ahmed, Dr. Sameer Hameed, Dr. Mustafa Hameed, and Dr. Ali Saood.

xix

Contents

1 Embryology of the Pineal Gland��������������������������������������������������������������   1 Alexis Rafael Narváez-Rojas, Juan Bosco González-Torres, Ali A. Dolachee, and Ali Odai Mahmood 2 Anatomy of the Pineal Gland��������������������������������������������������������������������  11 Alexis Rafael Narváez-Rojas, Ali A. Dolachee, Aktham O. Alkhafaji, Mustafa E. Almurayati, Mohammed Ali Al-Dhahir, and Hayder R. Salih 3 Physiology of the Pineal Gland ����������������������������������������������������������������  21 Alexis Rafael Narváez-Rojas, Luis R. Moscote-Salazar, Ali A. Dolachee, Mohammed Ameen Alrawi, Ali M. Neamah, and Saja A. AlBanaa 4 Neuroimaging of the Pineal Gland ����������������������������������������������������������  31 Hernando Alvis-Miranda, Kalil Kafury-Benedetti, Osvaldo Molina-Olier, Fernando Ponce-Iglesias, and Mustafa Adnan Shamkhi 5 Tumors of the Pineal Gland����������������������������������������������������������������������  49 Abdullah Husain Al Ramadan, Sadeq Wasil Al-Dandan, and Muthanna Noaman Abdulqader 6 Non-tumorous Lesions of the Pineal Gland��������������������������������������������  77 Martin Majovsky 7 Treatment and Approaches for the Pineal Gland Region����������������������  93 Baha’eddin A. Muhsen, Hamid Borghei-Razavi, and Samer S. Hoz 8 Interesting Cases of Pineal Gland Diseases and Surgery ���������������������� 111 Gobran Taha Al-Fotih and Samer S. Hoz

xxi

xxii

Contents

9 Animal Based Surgical Training in Pineal Approaches�������������������������� 123 Samer S. Hoz, Rami Darwazeh, Mohammed Sabah Abdulqader, Osama Majeed Alaawadi, Gulshan Talat Muhammed, Awfa Aktham Abdullateef, Aysar Khudhair Jassam, Alyaa Khadim Abdulreda, and Hayder Ali Al-Saadi 10 Evolutionary Retrace of the Third Eye���������������������������������������������������� 133 Mohammed Maan Al-Salihi

Contributors

Mohammed  Maan  Al-Salihi  College of Medicine, University of Baghdad, Baghdad, Iraq Awfa Aktham Abdullateef  Department of Neurosurgery, Neurosurgery Teaching Hospital, Baghdad, Iraq Mohammed  Sabah  Abdulqader  Department of Neurosurgery, Neurosurgery Teaching Hospital, Baghdad, Iraq Muthanna  Noaman  Abdulqader  Department of Neurosurgery, Neurosurgery Teaching Hospital, Baghdad, Iraq Alyaa Khadim Abdulreda  Department of Neurosurgery, Neurosurgery Teaching Hospital, Baghdad, Iraq Abdullah  Husain  Al  Ramadan  Section of Neurosurgery, Department of Neurosciences, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia Osama Majeed Alaawadi  Department of Neurosurgery, Neurosurgery Teaching Hospital, Baghdad, Iraq Saja A. AlBanaa  College of Medicine, University of Baghdad, Baghdad, Iraq Sadeq  Wasil  Al-Dandan  Department of Pathology, Maternity and Children Hospital, Al-Ahsa, Saudi Arabia Mohammed  Ali  Al-Dhahir  Department of Neurosurgery, Yemeni German Hospital, Sana’a, Yemen Gobran Taha Al-Fotih  Department of Neurosurgery, Al-Thawra Modern General Hospital, Sana’a, Yemen Aktham O. Alkhafaji  College of Medicine, University of Baghdad, Baghdad, Iraq Mustafa  E.  Almurayati  College of Medicine, University of Baghdad, Baghdad, Iraq Mohammed Ameen Alrawi  Department of Neurosurgery, Neurosurgery Teaching Hospital, Baghdad, Iraq xxiii

xxiv

Contributors

Hayder  Ali  Al-Saadi  Department of Neurosurgery, Neurosurgery Teaching Hospital, Baghdad, Iraq Hernando Alvis-Miranda  Department of Neurosurgery, University of Cartagena, Colombian Foundation Center for Epilepsy and Neurological Diseases—FIRE, Cartagena, Colombia Kalil  Kafury-Benedetti  Colombian Foundation Center for Epilepsy and Neurological Diseases—FIRE, Cartagena, Colombia Hamid Borghei-Razavi  Department of Neurosurgery, Rose Ella Burkhardt Brain Tumor & Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA Rami  Darwazeh  Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Ali  A.  Dolachee  Department of Surgery, College of Medicine, University of Al-Qadisiyah, Diwaniyah, Iraq Juan Bosco González-Torres  Pediatric Neurosurgery, “Manuel de Jesus Rivera” Children’s Hospital, Hospital Bautista, Managua, Nicaragua Samer S. Hoz  Neurosurgery Teaching Hospital, Baghdad, Iraq Fernando  Ponce-Iglesias  Colombian Foundation Center for Epilepsy and Neurological Diseases—FIRE, Cartagena, Colombia Aysar  Khudhair  Jassam  Department of Neurosurgery, Neurosurgery Teaching Hospital, Baghdad, Iraq Meleine  Landry  Konan  Human Anatomy and Neurosurgery, University Felix Houphouet Boigny, Abidjan, Ivory Coast Ali  Odai  Mahmood  Department of Neurosurgery, Neurosurgery Teaching Hospital, Baghdad, Iraq Martin Majovsky  Department of Neurosurgery and Neurooncology, First Faculty of Medicine of Charles University, Military University Hospital, Prague, Czech Republic Luis R. Moscote-Salazar  Department of Neurosurgery, Cartagena Neurotrauma Research Group (CIB), University of Cartagena, Bolívar, Colombia Gulshan Talat Muhammed  Department of Neurosurgery, Neurosurgery Teaching Hospital, Baghdad, Iraq Baha’eddin A. Muhsen  Department of Neurosurgery, Rose Ella Burkhardt Brain Tumor & Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA Alexis Rafael Narváez-Rojas  Department of Surgery, Carlos Roberto Huembes Hospital, Managua, Nicaragua

Contributors

xxv

Ali M. Neamah  College of Medicine, University of Baghdad, Baghdad, Iraq Osvaldo  Molina-­Olier  Colombian Foundation Center for Epilepsy and Neurological Diseases—FIRE, Cartagena, Colombia Hayder R. Salih  Neurosurgery Teaching Hospital, Baghdad, Iraq Mustafa Adnan Shamkhi  Department of Neurosurgery, Neurosurgery Teaching Hospital, Baghdad, Iraq

Abbreviations

AANAT Aralkylamine N-acetyltransferase AFP Alfa-fetoprotein ASMT Acetyl-serotonin O-methyl transferase AT/RT Atypical teratoid/rhabdoid tumor AVM Arteriovenous malformation BBB Blood—brain barrier CEA Carcinoembryonic antigen CNS Central nervous system CSF Cerebrospinal fluid CT Computed tomography DWI Diffusion-weighted imaging EC Embryonal carcinoma GABA Gamma aminobutyric acid GBM Glioblastomas multiform GCT Germinal cell tumor GFAP Glial fibrillary acidic protein GRE Gradient echo hCG Human chorionic gonadotropin HIOMT Hydroxyindole-O-methyltransferase HPL Human placental lactogen ICP Intracranial pressure IHPO Interhemispheric parieto-occipital approach IL Interleukin SCIT The supracerebellar infratentorial LPA Lateral pineal artery MEL1 Melatonin receptor type 1 MHCII Major histocompatibility complex type II MPA Medial pineal artery MPCHA Medial posterior choroidal artery MRI Magnetic resonance imaging MRS Magnetic resonance spectroscopy MTNR Type of melatonin receptor found in specific chromosomes NAA N-acetyl-aspartate NAS N-acetyl serotonin xxvii

xxviii

NECT Non-enhanced CT OTT Occipital transtentorial approach OTX2 Orthodenticle homeobox 2 PC Pineal cyst PCNA Proliferating cell nuclear antigen PG Pineal gland PLAP Placental alkaline phosphatase PNB Pineoblastomas PNET Primitive neuroectodermal tumors PPT Pineal parenchymal tumors PPTID Pineal parenchymal tumors of intermediate differentiation PRT Pineal region tumor PTPR Papillary tumors of the pineal region RPA Rostral pineal artery SCIT Supracerebellar infratentorial approach SRS Stereotactic radiosurgery SWI Susceptibility-weighted imaging TNF-R1 Tumor necrotic factor R1 VOG Vein of Galen VIP Vasoactive intestinal peptide WHO World Health Organization YST Yolk sac tumor

Abbreviations

1

Embryology of the Pineal Gland Alexis Rafael Narváez-Rojas, Juan Bosco González-Torres, Ali A. Dolachee, and Ali Odai Mahmood

1.1

Introduction

The mammalian pineal gland (PG) can be considered as an indirectly photosensory neuroendocrine organ with the restriction that its secretory cells are not nerve elements but are phylogenetically transformed neuro-sensory photoreceptor cells derived from the embryonic neuroepithelium. Factors that contribute to the embryonic development of the pineal gland have not been completely elucidated, nor have pineal cell lineages been well characterized. The development of the pineal gland of mammals has been described in rats, hamsters, cows, squirrels of the Indian palm, rabbits, and Dasyurus hallucatus. Pax6+ could be a precursor to most types of cells found in the adult pineal gland, except for microglial cells. Microglial cells come from the mesoderm and play a prominent role in the developing pineal gland and the adult pineal gland. The human pineal gland grows in size until about 1–2 years of age, remaining stable thereafter, although its weight increases gradually from puberty onward. In the younger embryos, the comparatively large anlage of the posterior commissure forms the chief factor in the orientation of the gland. This commissure is easily recognizable by its histological appearances.

A. R. Narváez-Rojas (*) Department of Surgery, Carlos Roberto Huembes Hospital, Managua, Nicaragua J. B. González-Torres Pediatric Neurosurgery, “Manuel de Jesus Rivera” Children’s Hospital, Hospital Bautista, Managua, Nicaragua A. A. Dolachee Department of Surgery, College of Medicine, University of Al-Qadisiyah, Diwaniyah, Iraq e-mail: [email protected] A. O. Mahmood Department of Neurosurgery, Neurosurgery Teaching Hospital, Baghdad, Iraq © Springer Nature Switzerland AG 2020 S. S. Hoz et al. (eds.), Pineal Neurosurgery, https://doi.org/10.1007/978-3-030-53191-1_1

1

2

A. R. Narváez-Rojas et al.

The anterior pineal anlage increases in size between the third and fourth months of intrauterine life and embraces the habenula. Continuous with the third ventricle, the pineal diverticulum gets invested by the posterior anlage which joins the posterior commissure as it projects into the ventricle. There is no discernible line of demarcation between the two anlagen cells. Even at this point, it was evident that the diverticulum was constricted by the compression of the two anlagen. Through projection of vascular connective tissue into the periphery of the pineal gland, the vascularization starts within the mid-intrauterine life. The posterior commissure’s neuroglial network continues into the pineal mass. The elongated pale nuclei distinguish the connective tissue components. The structure of the pineal is similar to that of post-natal glands in parts of embryos during the later months of intrauterine development. The pineal recess, lined by ependyma, projects into the pineal anteriorly and is embraced by the neuroglial peduncles. At many points, vascular connective tissue enters the periphery of the organ and the connective tissue septum is observed originally separating the two pineal anlagen. The pineal peduncle neuroglial network invades the cellular mass and joins an already present similar network in the gland. The undifferentiated pineal cells were transformed into the so-called pineal parenchyma during the eighth fetal month. During fetal life, the primitive pineal diverticulum is reduced to the pineal recess and cavum pineale. The PG was found to assume characteristics during infancy that more or less persist throughout life. The parenchymatic mass was mounted over the third ventricle’s backward extension, i.e., the pineal recess. The PG was extended forward embracing the pineal recess and forming the peduncles of the pineal. The PG is enveloped by a capsule derived from the pia mater and peripherally invaded with fine blood vessels. The predominance of glia at this age and the marked reduction in the amount of parenchyma appear to contradict the previous belief that glia gradually replaces pineal cells as age progresses. “Loculation” of the PG by fibroglial trabeculae is present in most adult PGs. This may be part of the normal fibrosis consequent on advancing years and is seen in other organs such as the pituitary gland. The blood supply of the PG is not rich compared to that of the better-known endocrine organs. Most of the PG’s embryology information was obtained through mammalian studies. Therefore, the findings obtained from animal studies are of crucial importance, owing to the scarcity of human-based studies. The importance of studying the embryology of the PG is a challenge for the neurosurgeon, since this gland may be the anatomical site for development of neoplasms that develop as early as the embryonic period.

1  Embryology of the Pineal Gland

1.2

3

The Embryological Stages of the Pineal Gland

1.2.1 Stage 1: Morphogenic • In mammals, this stage starts on a day between 12 and 30 days of intrauterine development. It begins as an initial sketch located in the midline of the diencephalon between the habenular and posterior commissures [1, 2]. • The Pax6+ precursor factor is necessary for the initiation of the primordium formation, pineal sketch, or evagination and subsequent development of the pineal gland. The homeobox gene Lhx9 controls the development of the pineal gland [2, 3]. • The pineal primordium develops from the neuroectoderm and the oral ectoderm. Initially, the pineal primordium consists of radially aligned Pax6+ cells, which express vimentin and divide into the ventricular lumen. In this early stage, the pineal recess appears, which connects to the third ventricle [2–5]. • Around the 40th day of intrauterine development, there is a stratified epithelium that derives from ependymal cells which covers the pineal primordium. This stratified epithelium is composed of morphologically round cells with round or oval nuclei with abundant mitotic phenomena [2–6]. • The pineal epithelium at this stage shows no morphological differences with the neuroepithelium, and its apical border is well delimited and with few cellular elements. There is extensive vascularization mainly at the base of the pineal epithelium, from where the capillaries penetrate to the interior [4–6]. • As development progresses, around day 52 of gestation, the pineal outline appears more developed perpendicularly, showing extensive communication with the pineal recess. Later the pineal epithelium appears compressed, showing high cellular density [3–6].

1.2.2 Stage 2: Proliferative • During this phase, the migration of different cellular precursors of the pineal gland occurs in adulthood. • Pineoblasts and spongioblasts are derived from the pseudostratified epithelium covering the pineal primordium. Pinealocytes and astrocytes are derived from pinealoblasts and spongioblasts, respectively. The Pax6+ precursors generate pinealocytes and interstitial cells, respectively, the pinealocytes comprising approximately 95% of all cells later in the adult stage. • Schwannocytes and melanocytes are derived from the neural crest.

4

A. R. Narváez-Rojas et al.

• Fibroblasts, endothelial cells, and mast cells develop from the meningeal mesenchyme. • Microglial cells have been identified based on OX6 (MHCII), OX42 (CD11b), IL-1β, ED1 (CD68), and TNF-R1 markers. • The microglia begin to colonize the pineal neuroepithelium before the pinealocytes have differentiated. Microglia seems to populate the pineal primordium of the meninges and also the choroidal plexus of the pineal primordium. Most pineal microglia express the PCNA mitotic marker. The microglia in the development of the pineal gland excite an activated morphology. • A distinctive characteristic in this phase is the presence of cisterns or rosettes that present a small circular light and lack content. • The tubular neuroepithelium is subsequently fused and the distribution of Pax6+ cells can include scattered cells at this time. • All of the above allows the glandular contour to approach its definitive shape, showing a compact rounded shape that penetrates to the cerebral-cerebellar area. • A progressive growth follows a reduction in the volume of the pineal recess which stays connected to the third ventricle. • Both the habenular and posterior commissures appear well differentiated. • The pineal epithelium appears well developed, with abundant cells that are characterized by elongated nuclei. The inner region of the pineal parenchyma is the dominant zone in terms of size and extension. • The pineal recess penetrates the interior of the pineal primordium. • Once the morphology and development of microglia have been completed in many areas of the brain, the cells acquire a resting state [7–16].

1.2.3 Stage 3: Glandular Hypertrophy • In this phase, the development of the pineal gland is completed with two areas that can be clearly distinguished: the cortical and medullary zone. • The pinealoblasts begin to emit nerve extensions and change their rounded shape. • The septa are composed of reticular fibers formed with abundant blood flow. • Vascularization comes from the posterior choroidal arteries of the posterior cerebral arteries that surround and penetrate the pineal capsule. • The venous drainage comes to flow into a thick vessel that, after joining the vein of Galen, empties into the anterior portion of the straight sinus. • The pigment distribution of the gland is maintained, and less pigment is found at the distal end while the greater one at the proximal end. The pigment of the pineal gland is similar to that of melatonin. • The pineal gland is innervated mainly by the pineal nerve of sympathetic superior cervical ganglion. The gestational age at which the pineal nerve degenerates is not yet determined.

1  Embryology of the Pineal Gland

5

Table 1.1  Phases of the development of the pineal gland Stage Morphogenic

Proliferative

Glandular hypertrophy

Feature • First glandular outline differentiates from diencephalic ependyma of the third ventricle • High mitotic activity • Vascularization at the base • Perpendicularization of pineal gland • Pinealoblasts and interstitial cells begin to differentiate • Glandular stroma develops from connective tissue that surrounds and penetrates in a trabecular fashion • Mesenchyme development • Microglia begins to colonize forming the pineal neuroepithelium • Resting state at the end • NPY-positive fibers enter into the gland and are distributed perivascularly • Glial fibrillary acidic protein (GFAP)-positive cells • Pinealoblasts begin to emit nerve extensions • Vascularization from posterior cerebral arteries • The presence of pineal or fetal nerve • Degeneration of pineal nerve at an unknown stage

• At the end of development, the mature PG is considered a relatively homogeneous organ and reaches a length of 7.4 mm, width of 6.9 mm, height of 2.5 mm, and a volume of 207 mm3 (17.5 times greater than the volume of pineal primordium) [15–22] (Table 1.1).

1.3

Clinical Applications

As the primordial germ cells migrate from the wall of yolk sac toward the developing gonads, some primitive germ cells aberrate into other sites in this migration stage. Extragonadal germ cell tumors (GCTs) may develop even in the central nervous system. The embryonal carcinomas as tumors of totipotent cells that may give rise to either embryonal neoplasms, with the potential to differentiate into the derivatives of all three germ layers (teratoma), or extraembryonic neoplasms (yolk sac tumor and choriocarcinoma), thus the histology of intracranial GCTs is similar to that of GCTs elsewhere in the body [5, 9, 21].

1.4

Summary

Three phases of the development of the pineal gland have been described. Morphogenetic phase: this begins approximately at day 30 of the intrauterine development with an initial outline, located in the median line of the roof of the diencephalon between the habenular and posterior commissures. The pineal recess

6

A. R. Narváez-Rojas et al.

has a large volume connected to the third ventricle. Proliferative phase: during this stage, the migration of the different cellular precursors of the gland in adult state takes place. After cellular migration, the gland acquires a more compact appearance, and finally the obliteration of the pineal recess occurs due to mechanical phenomena (space limitation) and the presence of abundant mitosis, all this around day 98 of the intrauterine development. Glandular hypertrophy phase: around day 118 the maturation of the gland is completed, in which two clearly differentiated zones can be distinguished, the medullary and cortical zones. The literature on embryology of the pineal gland is scarce. Through this chapter we try to present the different investigations that have been made in mammals about new cellular and molecular aspects found in the different stages mainly in the proliferative phase. Questions on the Embryology of the Pineal Gland 1. In morphogenic stage of pineal gland development: A. High mitotic activity. B. Pax6+ initiation factor. C. Vascularization at the base. D. Lhx9 control factor. E. All of the above are true. 2. In proliferative stage of pineal gland development: A. Pinealoblasts and interstitial cells begin to differentiate. B. Mesenchyme development. C. Glandular stroma develops from connective tissue that surrounds and penetrates in a trabecular fashion. D. Resting state. E. All are true. 3. In glandular hypertrophy stage of pineal gland development: A. Pinealoblasts begin to emit nerve extensions. B. Vascularization from posterior cerebral arteries. C. Neuropeptide Y-positive fibers enter into the gland and are distributed perivascularly. D. All of the above. E. None of the above. 4. Perpendicularization of pineal gland occurs in which developmental stage: A. Morphogenic stage B. Proliferative stage C. Glandular hypertrophy stage D. Vascular stage E. None of the above

1  Embryology of the Pineal Gland

7

5. Which of the following is FALSE? A. The cortical and medullary zones appear in glandular hypertrophy phase. B. Blood supply of the PG comes from the posterior choroidal arteries. C. Venous drainage empties into the anterior portion of the straight sinus. D. PG is innervated by sympathetic supply from the superior cervical. E. The development of the PG is completed in the morphogenic phase. 6. Which of the following is TRUE regarding the glandular hypertrophy phase? A. Vascularization from posterior cerebral arteries. B. Mesenchyme development. C. Resting state. D. First glandular outline differentiates from diencephalic ependyma of the third ventricle. E. Glandular stroma form trabecula. 7. Microglia begins to colonize the pineal neuroepithelium occurs in which stage of pineal gland development: A. Morphogenic stage B. Proliferative stage C. Glandular hypertrophy stage D. Vascular stage E. None of the above 8. First glandular outline differentiates from diencephalic ependyma of the third ventricle occurs in which stage of pineal gland development: A. Morphogenic stage B. Proliferative stage C. Glandular hypertrophy stage D. Vascular stage E. None of the above 9. Glial fibrillary acidic protein (GFAP)-positive cell colonization occurs in which stage of pineal gland development: A. Morphogenic stage B. Proliferative stage C. Glandular hypertrophy stage D. Vascular stage E. None of the above

8

A. R. Narváez-Rojas et al.

Answers 1. E. 2. E. 3. D. 4. A. 5. E. 6. A. 7. B. 8. A. 9. C.

References 1. Brainard GC, Hanifin JP, Greeson JM, Byrne B, Glickman G, Gerner E, Rollag MD. Action spectrum for melatonin regulation in humans: evidence for a novel circadian photoreceptor. J Neurosci. 2001;21(16):6405–12. 2. Garcia J, Sicila C. Embryonic development of the rabbit pineal gland (Oryctolagus Cuniculus) (Lagomorpha). Eur J Anat. 2001;5:55–66. 3. Quay WB. Pineal canaliculi: demonstration, twenty-four-hour rhythmicity and experimental modification. Am J Anat. 1974;139(1):81–93. 4. Regodón S, Roncero V. Embryonic development of the bovine pineal gland (Bos taurus) during prenatal life (30 to 135 days of gestation). Histol Histopathol. 2005;20(4):1093–103. 5. Rodriguez MP, Noctor SC, Muñoz EM. Cellular basis of pineal gland development: emerging role of microglia as phenotype regulator. PLoS One. 2016;11(11):e0167063. 6. Møller M, Møllgård K, Kimble JE. Presence of a pineal nerve in sheep and rabbit fetuses. Cell Tissue Res. 1975;158(4):451–9. 7. Bhatnagar KP.  Synaptic ribbons of the mammalian pineal gland: enigmatic organelles of poorly understood function. Adv Struct Biol. 1994;3:47–94. 8. Boya J, Calvo JL. Immunohistochemical study of the pineal astrocytes in the postnatal development of the cat and dog pineal gland. J Pineal Res. 1993;15(1):13–20. 9. Roa I, del Sol M. Morfología de la Glándula Pineal: Revisión de la Literatura. Int J Morphol. 2014;32(2):515–21. 10. Moore RY. Neural control of the pineal gland. Behav Brain Res. 1995;73(1–2):125–30. 11. Regodón S, Franco AJ, Gazquez A, Redondo E. Presence of pigment in the ovine pineal gland during embryonic development. Histol Histopathol. 1998;13(1):147–54. 12. Calvo J, Boya J.  Embryonic development of the rat pineal gland. Anat Rec. 1981;200(4):491–500. 13. Anderson CR, Penkethman SL, Bergner AJ, McAllen RM, Murphy SM. Control of postganglionic neurone phenotype by the rat pineal gland. Neuroscience. 2002;109(2):329–37. 14. Calvo J, Boya J, García-Mauriño JE, Lopez-Carbonell A. Postnatal development of the dog pineal gland: electron microscopy. J Pineal Res. 1990;8:245–54. 15. Nishida A, Furukawa A, Koike C, Tano Y, Aizawa S, Matsuo I, Furukawa T.  Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development. Nat Neurosci. 2003;6(12):1255. 16. Altar A. Development of the mammalian pineal gland. Dev Neurosci. 1982;5:166–80. https:// doi.org/10.1159/000112673. 17. Ziv L, Levkovitz S, Toyama R, Falcon J, Gothilf Y. Functional development of the zebrafish pineal gland: light-induced expression of period2 is required for onset of the circadian clock. J Neuroendocrinol. 2005;17(5):314–20.

1  Embryology of the Pineal Gland

9

18. Mehmet Turgut AUMY.  Morphological characteristics and embryological development of pineal gland and experimental grafting procedures. Arch Med Rev J. 2003;12:65–76. 19. Jové M, Cobos P, Torrente M, Gilabert R, Piera V. Embryonic development of pineal gland vesicles: a morphological and morphometrical study in chick embryos. Eur J Morphol. 1999;37(1):29–35. 20. Møller M.  Presence of a pineal nerve (nervus pinealis) in fetal mammals. Prog Brain Res. 1979;52:103–6. 21. Møller M, Phansuwan-Pujito P, Badiu C. Neuropeptide Y in the adult and fetal human pineal gland. Biomed Res Int. 2014;2014:1. 22. Vollrath L.  Comparative morphology of the vertebrate pineal complex. Prog Brain Res. 1979;52:25–38.

2

Anatomy of the Pineal Gland Alexis Rafael Narváez-Rojas, Ali A. Dolachee, Aktham O. Alkhafaji, Mustafa E. Almurayati, Mohammed Ali Al-Dhahir, and Hayder R. Salih

2.1

Introduction

• The pineal gland (PG) is a unique, small-sized endocrine organ. • It forms an appendix from the caudal end of the diencephalon that includes the pineal recess of the third ventricle. • The pineal region includes the PG inside the quadrigeminal cistern. • The PG is surrounded by several important structures such as the posterior part of the third ventricle, the cerebral vein of Galen complex, the thalamus, and the splenium of the corpus callosum.

2.2

Gross Anatomy of the Pineal Gland

The pineal gland is a small reddish-gray structure, composed of gray matter. • The pineal gland is essentially an extra-axial structure and it is surrounded by: –– The posterior commissure ventrally

A. R. Narváez-Rojas (*) Department of Surgery, Carlos Roberto Huembes Hospital, Managua, Nicaragua A. A. Dolachee Department of Surgery, College of Medicine, University of Al-Qadisiyah, Diwaniyah, Iraq e-mail: [email protected] A. O. Alkhafaji · M. E. Almurayati College of Medicine, University of Baghdad, Baghdad, Iraq M. A. Al-Dhahir Department of Neurosurgery, Yemeni German Hospital, Sana’a, Yemen H. R. Salih Neurosurgery Teaching Hospital, Baghdad, Iraq © Springer Nature Switzerland AG 2020 S. S. Hoz et al. (eds.), Pineal Neurosurgery, https://doi.org/10.1007/978-3-030-53191-1_2

11

12

A. R. Narváez-Rojas et al. Choroid plexus Corpus Callosum

Pineal gland

Fornix

Tentorium

Fig. 2.1  Median sagittal section showing the cranial relation of the pineal gland (© Meleine Landry Konan, Neurosurgeon, University Felix Houphouet Boigny, Ivory Coast)

• • • •

• • • • • •

–– The corpus callosum superiorly –– The habenular commissure dorsally (Figs. 2.1 and 2.2) It is completely covered by pia mater and bathed by cerebrospinal fluid. The pia mater forms a capsule from which partitions are projected through which numerous blood vessels enter. These partitions will later divide them into incomplete lobules. Both conical and oval shapes of the PG have been described. PG weight and volume vary greatly in respect of time, age, and physiological condition. Its mean size is 7.4 mm in length, 6.9 mm in width, and 2.5 mm in thickness. The mean weight of the adult human pineal gland is generally 50–150 mg. It is located between the diencephalon and mesencephalon at the level of the incisura of the tentorium cerebelli. PG is directed antero-posteriorly and rests on the groove that separates the superior colliculi from the posterior wall of the third ventricle. It is attached to the habenular commissure and posterior commissure by a peduncular formation called the “pineal stem.” The posterior portion of the corpus callosum, splenium, is superimposed on the PG. Although the PG is suspended in the pineal recess, it is surrounded by a pial layer. The velum interpositum, which incorporates the internal cerebral veins and the choroid plexus, is intimate with the dorsal surface of PG [1–9].

2  Anatomy of the Pineal Gland Corpus callosum

13 Fornix

Choroid plexus

Internal cerebral vein

Pineal gland Superior colliculus

Midbrain

Fourth ventricle

Cerebellum

Fig. 2.2  Median sagittal section showing the pineal gland and the related structures (© Luis R. Moscote-Salazar, Department of Neurosurgery, University of Cartagena, Colombia)

2.3

Growth Pattern

• There is no consensus regarding the volume of the pineal gland in humans. • Pineal gland grows in size from birth until 2 years of age and then remains constant between 2 and 20 years of age [5, 9].

2.4

Ventricular Relations

• Cranially the pineal gland is in relation to the pineal and suprapineal recesses of the third ventricles. The pineal recess is in continuity with the posterior part of the third ventricle and provides access to the anterior part of PG. The suprapineal recess may contain choroidal plexuses.

14

A. R. Narváez-Rojas et al.

• The superior opening of cerebral aqueduct is located in front of the posterior commissure and located antero-inferior to the PG. • The roof of the third ventricle is triangular and has a posterior base with a posterior extension between the two thalami, formed by an ependymal membrane condensed into two formations: –– The tectorial membrane of the third ventricle –– The choroid tissue • The PG is separated from the splenium of the corpus callosum by the choroid tissue [9, 10].

2.5

Posterior Incisural Space

• The distance between the posterior limits of the tentorial notch and the tentorial body varies from 10 to 30 mm. • The variation of the distance described above could influence the time of making a choice of the surgical approach [10–13].

2.6

Vascularization

• The pineal gland represents a copious vascularization that blood flow has been established to be approximately 4 mL/min. • The blood flow in the pineal gland is much higher than in any other endocrine gland, equating to the neurohypophysis and surpassed only by the kidney. • The posteromedial and postero-lateral choroidal arteries are contributing to the great vascularization through anastomoses to the pericallosal, posterior cerebral, superior cerebellar, and quadrigeminal arteries. • PG is arterialized by three arterial groups: –– Lateral pineal artery (LPA) –– Medial pineal artery (MPA) –– Rostral pineal artery (RPA) • LPA and MPA are consistently derived from the posterior circulation, while the RPA originates from either posterior or anterior circulation. • Arterial supply of the PG is provided mainly by branches deriving from the MPCHA (medial posterior choroidal artery). This artery penetrates the PG from its lateral side. And its branches to the PG usually originate from the MPCHA at the ambient cistern. • Lateral pineal artery: In around 60%, these derived from the medial posterior choroidal artery (MPCHA). Other possible origins may be the superior cerebellar artery (SCA) and the lateral posterior choroidal artery. Especially the lateral region of the PG was vascularized by branches deriving from the lateral side. In around 70%, the LPA is the main artery providing the arterial supply of the PG, and the mean diameter was 0.22 mm.

2  Anatomy of the Pineal Gland

15

• Medial pineal artery: The MPA is not a constant branch (only 33%), and when present it is usually formed by branches coursing through the midline and f­ eeding the apex of the PG. This arterial group usually originates from the MPCHA; rarely it is derived from the SCA.  The average diameter is 0.22 mm. • Rostral pineal artery: This artery presents in only 21% with the general average diameter at 0.17 mm. It usually courses through the superior aspect of the PG and provides blood to the circulation. Unlike other arteries of the PG, this artery branches from the anterior, instead of the posterior circulation. Most frequently, branches from the A5 segment of the anterior communicating artery (ACA) supply the vasculature. Another possible origin is from A4. Posterior circulation develops from the MPCHA or the P3. • The medial posterior choroidal artery: The MPCHA arises from the P-2A segment in 57.5% of the specimens, but occasionally arises from P-I (13.5%), P-2P (13.5%), P-3 (7.7%), or the cortical branches (7.7%). It runs parallel and usually medial to the PCA and courses to the quadrigeminal cistern. The MPCHA lay lateral to the PG and courses in the roof of the third ventricle parallel and medial to the internal cerebral vein in the midline and finally supplies the choroid plexus of the third ventricle at the foramen of Monro. Along its course, the MPCHA sends an average of 1.5 branches to the PG (zero to five). • The choroidal arteries have a parallel distribution and are generally medial to the back of the brain; they also go laterally to the PG and travel through the roof of the third ventricle. • In addition to the PG, they also provide vascularization to the superior and inferior colliculi, choroidal plexus of the third ventricle up to the foramen of Monro. • The posterior lateral choroidal arteries arise in the posterior part of the incisural space and then through the choroidal fissure supplying the choroid [14, 15].

2.7

Venous Drainage System

• The implementation of Seven Tesla Magnetic Resonance Imaging (7  T MRI) gives a new and wider variation in the venous system of the pineal gland in relation to postmortem studies performed in humans previously. • There are gender differences in terms of venous structure in the pineal gland. • The pineal vein is a tiny structure, but it plays an important role in the human body. • Three types of vascular structure of the PG exist: –– Type I: The pineal vein drains directly into the great cerebral vein of Galen. –– Type II: The pineal vein drains into the internal cerebral vein. –– Type III: The pineal vein drains into the great cerebral vein of Galen and into the internal cerebral vein.

16

A. R. Narváez-Rojas et al.

• The upper pineal veins drain in the upper portion of the PG and the basal pineal veins drain in the lower region. • The sagittal projection of the PG has shown a tendency of the venous vascular structure type I in men and vascular structure type II in women. Meanwhile, vascular structure type III has presented the same trend in both sexes with no confirmed explanation for such a difference. • These variations in the venous structure of the PG could be considered an important factor related to the diagnoses of diseases and disorders [14, 15] (see Chap. 7).

2.8

Innervation

• The PG is innervated by sympathetic fibers originating in the central nervous system. • The main pathway of innervation is the superior sympathetic ganglion of the paravertebral chain. • This superior sympathetic ganglion is the main ganglionic affection that happens to form the pineal nerve. • Sympathetic postganglionic axons ascend along the internal carotid artery to enter the pineal nerve. • The pineal nerve is found in the cerebellar tentorium. • The first component of the innervation pathway of the PG is the retinohypothalamic tract (RHT). • The retinohypothalamic tract originates from the cells of the retinal ganglion until reaching the hypothalamus [16]. • Sympathetic –– Norepinephrine –– Neuropeptide Y (NPY) • Parasympathetic –– Pterygopalatine ganglion –– Otic ganglion –– Vasoactive intestinal peptide (VIP) –– Peptide histidine isoleucine (PHI) • Central innervation –– GABA –– Vasopressin and oxytocin • Trigeminal ganglion –– Substance P –– Calcitonin gene-related peptide (CGRP) pituitary adenylate cyclase-­activating peptide (PACAP)

2  Anatomy of the Pineal Gland

17

Questions Regarding the Anatomy of the Pineal Gland 1. Which of the following is FALSE: A. PG is an exocrine organ. B. PG forms an appendix of the caudal end of diencephalon. C. PG is found inside the quadrigeminal cistern. D. Surgical approach of the PG represents a neurosurgical challenge. E. Splenium of the corpus callosum is located superior to the PG. 2. Which of the following is TRUE: A. PG is composed of white matter. B. The arachnoid forms the capsule of PG. C. PG is either conical or oval in shape. D. The width of the gland is larger than its length. E. PG is anatomically located above the level of the tentorial incisura. 3. Which of the following is FALSE? A. PG is located between the superior colliculi and posterior wall of the third ventricle. B. PG is attached to the habenular commissure. C. The pineal stem is continuous with the habenular commissure dorsally. D. Although the gland is suspended in the pineal recess, it is surrounded by a pial layer. E. Splenium of the corpus callosum is found behind PG. 4. Which of the following is TRUE? A. PG has an inferior relation to the superior opening of the cerebral aqueduct. B. PG has no relation to the recesses of the third ventricles. C. There is no choroid plexus in the suprapineal recess. D. The tectorial membrane of third ventricle is limited by the posterior commissure. E. PG is separated from the splenium by the choroidal tissue. 5. Which of the following is FALSE? A. The blood flow in the PG is much higher than other endocrine gland. B. The greater vascularization is contributed by lenticulostriate arteries. C. Rostral pineal artery may originate from anterior circulation. D. PG is arterialized by lateral, medial, and rostral pineal arteries. E. PG blood flow is approximately 4 mL/min. 6. Which of the following is TRUE? A. Arterial supply of PG is provided mainly by branches from the lateral group of posterior choroidal artery. B. Branches supplying the PG are usually originating at the ambient cistern. C. In around 70%, the medial pineal artery is the main artery that provides the arterial supply of PG. D. Lateral pineal artery presents in only 21%. E. Rostral pineal artery most commonly originates from posterior cerebral artery.

18

A. R. Narváez-Rojas et al.

7. Which of the following is FALSE? A. Lateral pineal artery is derived from the MPCHA in around 20%. B. Lateral pineal artery is the main artery providing the arterial supply of the PG in 70%. C. Medial pineal artery is found in about 30% of people. D. Both medial and lateral pineal arteries have an average diameter of around 0.22 mm. E. Rostral pineal artery is found in 21% with average diameter of 0.17 mm. 8. Which of the following is TRUE? A. The least common parent vessel to the posterior medial choroidal artery is the P3 segment. B. In the roof of the 3rd ventricle, the MPCHA lies lateral to the internal cerebral vein. C. MPCHA sends a maximum of five branches to PG. D. MPCHA supplies to both superior and inferior colliculi. E. MPCHA has a course in the roof of the 4th ventricle. 9. Which of the following is TRUE? A. There is gender difference in the venous drainage structure of PG. B. The pineal vein may be drained by vein of Galen, internal cerebral vein, or both. C. The upper pineal veins drain the upper portion of PG and the basal pineal veins drain the lower region. D. The venous drainage comes together in a thick vessel that empties into the anterior portion of the straight sinus. E. All of the above. 10. Which of the following is FALSE? A. PG is innervated by sympathetic and parasympathetic nerve. B. The main pathway of sympathetic innervation is the superior sympathetic ganglion of the paravertebral chain. C. The pineal nerve is found in the cerebral tentorium. D. The first component of the innervation pathway of PG originates from the retinal ganglion. E. The first component of the innervation pathway of PG is the retinohypothalamic tract.

2  Anatomy of the Pineal Gland

19

Answers 1. A. 2. C. 3. E. 4. E. 5. B. 6. B. 7. A. 8. C. 9. E. 10. A.

References 1. Choudhry O, Gupta G, Prestigiacomo CJ. On the surgery of the seat of the soul: the pineal gland and the history of its surgical approaches. Neurosurg Clin N Am. 2011;22(3):321–33. 2. Simon E, Afif A, M’Baye M, Mertens P. Anatomy of the pineal region applied to its surgical approach. Neurochirurgie. 2015;61(2–3):70–6. 3. Vollrath L. The pineal organ. Berlin, Heidelberg: Springer; 1981. p. 665. 4. Shoja MM, Hoepfner LD, Agutter PS, Singh R, Tubbs RS. History of the pineal gland. Child’s Nerv Syst. Springer Berlin, Heidelberg; 2016;32(4):583–586. 5. Smith CUM. Descartes’ pineal neuropsychology. Brain Cogn. 1998;36(1):57–72. 6. Zrenner C. Theories of pineal function from classical antiquity to 1900: a history. Pinea Res Rev. 1985;3:1–40. 7. Lokhorst G-JC, Kaitaro TT. The originality of Descartes theory about the pineal gland. J Hist Neurosci. 2001;10(1):6–18. 8. Lopez-Munoz F, Marín F, Alamo C. The historical background of the pineal gland: I. from a spiritual valve to the seat of the soul. Rev Neurol. 2010;50(1):50–7. 9. Favaron PO, Mançanares CA, De Carvalho AF, Ambrósio CE, Leiser R, Miglino MA. Gross and microscopic anatomy of the pineal gland in nasua nasua–coati (linnaeus, 1766). Anat Histol Embryol. 2008;37(6):464–8. 10. Anderson CR, Penkethman SL, Bergner AJ, McAllen RM, Murphy SM. Control of postganglionic neurone phenotype by the rat pineal gland. Neuroscience. 2002;109(2):329–37. 11. Koshy S, Vettivel S.  Melanin pigments in human pineal gland. J Anat Soc India. 2001;50(2):122–6. 12. Calvo JL, Boya J, García-Mauriño JE, Rancaño D. Presence of melanin in the cat pineal gland. Acta Anat (Basel). 1992;145(1):73–8. 13. Lima EMM, Santiana MIS, Castro MB, Benedicto HG, Ferreira PM, Vianna ARCB.  Microstructure and morphoquantitative study of pineal gland in santa ines sheep/ Estudo morfoquantitativo e da microestrutura da glândula pineal em ovinos Santa Inês. Ars Vet. 2011;27(3):186–91. 14. Kahilogullari G, Ugur HC, Comert A, Brohi RA, Ozgural O, Ozdemir M, et al. Arterial vascularization of the pineal gland. Childs Nerv Syst. 2013;29(10):1835–41. 15. Zang-Hee C, Sang-Han C, Je-Gun C, Young-Bo K. Classification of the venous architecture of the pineal gland by 7 T MRI. J Neuroradiol. 2011;38:238–41. 16. Møller M, Baeres FM.  The anatomy and innervation of the mammalian pineal gland. Cell Tissue Res. 2002;309(1):139–50.

3

Physiology of the Pineal Gland Alexis Rafael Narváez-Rojas, Luis R. Moscote-Salazar, Ali A. Dolachee, Mohammed Ameen Alrawi, Ali M. Neamah, and Saja A. AlBanaa

3.1

Introduction

• The descriptions of the pineal gland go back to antiquity, but its functions in humans are little known. • The pineal gland exerts its effect on human physiology through a variety of functions such as endocrine gland, hormone regulator, and as circadian rhythm. • The PG has a principal action of secreting hormones, mainly the melatonin. • Melatonin is secreted according to the presence of stimuli from the external environment through light changes. • These stimuli directly affect the activity of the pinealocyte activating it in the dark phase to secrete melatonin. • The physiological significance of pineal characters other than melatonin and pineal peptides has not yet been thoroughly understood.

A. R. Narváez-Rojas (*) Department of Surgery, Carlos Roberto Huembes Hospital, Managua, Nicaragua L. R. Moscote-Salazar Department of Neurosurgery, Cartagena Neurotrauma Research Group (CIB), University of Cartagena, Bolívar, Colombia A. A. Dolachee Department of Surgery, College of Medicine, University of Al-Qadisiyah, Diwaniyah, Iraq e-mail: [email protected] M. A. Alrawi Department of Neurosurgery, Neurosurgery Teaching Hospital, Baghdad, Iraq A. M. Neamah · S. A. AlBanaa College of Medicine, University of Baghdad, Baghdad, Iraq © Springer Nature Switzerland AG 2020 S. S. Hoz et al. (eds.), Pineal Neurosurgery, https://doi.org/10.1007/978-3-030-53191-1_3

21

22

3.2

A. R. Narváez-Rojas et al.

Physiological Aspects of the Pineal Gland

3.2.1 Synthesis of Melatonin • Classically, the synthesis of pineal melatonin involves the conversion of serotonin to N-acetyl serotonin (NAS) by the phosphorylated form of aralkylamine N-acetylphosphorylase (P-AANAT) and the methylation of NAS to melatonin (N-acetyl-5-methoxytryptamine) by the enzyme acetylserotonin O-­methyltransferase (ASMT) [1]. • The transcription of AANAT and phosphorylation of AANAT are regulated daily, while the activity of ASMT is regulated on a seasonal basis. • The phosphorylation of AANAT by protein kinase A (PKA) is mediated by the sympathetic stimulation of the adrenoceptor-1 of the pinealocytes [1, 2]. • However, the inhibition of adrenoceptor-1 completely suppresses the synthesis of pineal melatonin induced by sympathetic stimulation [3].

3.2.2 Melatonin Receptors • Melatonin receptors are found in different locations in the PG. • The main locations in which melatonin receptors are found are the brain, retina, cardiovascular system, cardiac ventricular wall, aorta, cerebral and coronary arteries, liver and gallbladder, colon, cecum, vermiform appendix, skin, parotid gland, ovaries, myometrium, placenta, and fetal kidney. • In the gastrointestinal system, melatonin receptors are found most frequently in the jejunal and colonic mucosa [3, 4]. • There are three different membrane receptors and a nuclear receptor. –– Melatonin receptor type 1a: Mel 1a, ML1a, ML1, MT1, and MTNR1A– It is encoded on human chromosome 4 and consists of 351 amino acids. –– Melatonin receptor type 1b: Mel 1b, ML1b, MT2, and MTNR1B– It is encoded in the human chromosome 11 and consists of 363 amino acids. –– Mel1c and MTNR1C: Not present in humans. It is found in fish, amphibians, and birds. –– MT3 and ML2 = NQO2 = quinone reductase 2 enzyme = QR2. This enzyme belongs to the reductase group, which participates in the prevention of oxidative stress by inhibiting the electron transfer reactions of the quinones. This enzyme (or MT3 receptor) is found in the liver, kidney, heart, lung, intestine, muscle, and brown fatty tissue. It is a detoxification enzyme. There is evidence of its participation in the regulation of intraocular pressure. –– RZR/RORα: nuclear hormone receptor related to the retinoid. With this receptor, melatonin binds to transcription factors in the nucleus that belong to the retinoic acid receptor superfamily [4, 5]. –– GPR50: H9, ML1X: orphan receptor related to melatonin. Linked to the coupled orphan protein G which is an inherited receptor linked to X. It is the

3  Physiology of the Pineal Gland

23

orthologue of MEL1c, which is found in nonmammalian living beings. Its gene is located in the X chromosome (Xq28) and consists of 618 amino acids. It is present in all mammals.

3.2.3 Mechanism of Effects of Melatonin • Melatonin shows its effects by many mechanisms including: –– Union to melatonin receptors in the plasma membrane –– Binding to intracellular proteins such as calmodulin –– Union to orphan nuclear receptors –– Antioxidant effect • Melatonin interacts with intracellular proteins called calmodulin, calreticulin, and tubulin. Calmodulin is a secondary intracellular messenger. Melatonin directly antagonizes the binding of calcium to calmodulin. The antiproliferative effect of cancer may be related to the above. • The family of hormone receptors related to the retinoid (RZR/ROR) is responsible for the immunomodulatory effects of melatonin. IL-2 and IL-6 are produced in mononuclear cells by this mechanism [1–7].

3.2.4 Seasonal Cycles • In most vertebrates, seasonal variations in photoperiod duration lead to opposite changes in pineal melatonin nighttime secretion. The duration of the melatonin secretory episode transmits information of the diurnal duration. • Individuals living in northern latitudes show melatonin elongation with peaks during winter nights. In the same way, the shortening of the results of the photoperiod in summer produces a lengthening of the melatonin signaling [6–9].

3.2.5 Circadian Rhythm • The concept of melatonin acting as an endogenous circadian rhythm regulator is based mainly on rodent research. • The rhythmic secretion of melatonin by the pineal gland is the best description of the circadian clock. The circadian activity reflects the rhythmic pattern of expression of central genes, called clock genes. Clock genes are regulated transcriptionally, translationally and post-translationally by self-regulating feedback loops. • The size and direction of phase changes depend on the phase (time of day) of melatonin administration. Timed administration of melatonin has been used successfully to facilitate readjustment after acute phase changes of schedules. Melatonin is useful to stabilize sleep in some cases [10–12].

24

A. R. Narváez-Rojas et al.

3.2.6 Melatonin and Associated Pathologies • Melatonin is secreted at night. Its maximum level in the dark is related to age and various diseases. • It performs a regulation on the performance of the sleep-wake cycle, influences the development of puberty, is related to seasonal adaptation, has effects on memory by directly affecting hippocampal neurons, and presents associations with the control of body posture and balance. • It has antinociceptive, anxiolytic, and antineophobic effects. • It acts in the locomotive activity. • It provides neuroprotection, reduction of blood pressure, modulation of pain [8–13].

3.2.7 Sleep • There are temporary associations between melatonin, body temperature, and sleep. • The ascent of seclusion of melatonin in the afternoon and precedes the usual around 2 hours before going to bed is believed to act as a blocking mechanism for sleep onset. • The production peak of melatonin coincides with nighttime depression in body temperature [6–14].

3.2.8 Association with Insomnia • Low melatonin during the night could be the cause of primary insomnia. • The direct relationship between endogenous melatonin production and insomnia can be proportional. • Melatonin facilitates sleep through an inhibitory action in the CNS. • Melatonin promotes the waking state during the afternoon. • The production of melatonin is not concomitant with aging [8–15].

3.2.9 Melatonin and Body Temperature • The administration of melatonin is followed by a decrease in core body temperature and skin temperature. • In healthy men and women, the suppression of nocturnal melatonin levels is accompanied by a rise in core body temperature. • The endogenous melatonin contributes to the nocturnal decrease in body temperature [16–18].

3  Physiology of the Pineal Gland

25

3.2.10 Reproductive Function • The relationship between the function of the PG and human reproduction was established more than a century ago. • A causal relationship between the onset of puberty and the decrease in pineal melatonin at this stage has been suggested. • Elevated levels of melatonin may be present in women with stress-induced exercise or hypothalamic hypogonadism. • Inhibition of sperm motility in normal semen has also been observed after melatonin administration [17, 18].

3.2.11 Cardiovascular System • There is a well-known diurnal variation in cardiovascular function. • It presents with low blood pressure, increased heart rate, cardiac output, and peripheral vascular resistance at night with high levels of melatonin. • There is an increased risk of myocardial involvement, a cerebrovascular accident during the morning coinciding with melatonin levels. • A hypotensive effect of melatonin has been demonstrated under normal conditions [15–18].

3.2.12 Immune System and Cancer • Chronic administration of melatonin increases the activity of helper T cells and production of IL-2. • Melatonin has been shown to be a more powerful antioxidant than glutathione, mannitol, or vitamin E. • Melatonin could act directly in carcinogenesis. • The oncostatic effect of melatonin is especially pronounced with dependent reproductive hormones (breast and ovary) [16–19].

3.2.13 Impact of Melatonin on the Development of the Nervous System • Melatonin receptors are highly expressed in embryos suggesting the role of this hormone during development. • The administration of melatonin has a general effect on cell proliferation. • Melatonin promotes cell division [19].

26

A. R. Narváez-Rojas et al.

3.2.14 Impact of Melatonin on Memory Formation • Melatonin most likely controls how quickly memory is acquired. • Melatonin does not control the consolidation and recovery phases. • Melatonin inhibits the modifications of the synaptic force that constitutes the basic cellular mechanism for memory [18].

3.2.15 Psychiatric and Neurological Disorders • Changes in melatonin levels have been reported in several psychiatric and neurological disorders. • Low nocturnal melatonin has been linked to depressive disorders and dysthymia. • The decrease in melatonin production has also been associated with fibromyalgia. • Pathological changes in the biological rhythm of melatonin have been hypothesized in chronic schizophrenia. • Decreased levels of melatonin have been observed after an ischemic cerebrovascular accident, acute cerebral hemorrhage, and aneurysm rupture. • There are indications of participation of pineal melatonin in the development of senile dementia, particularly Alzheimer’s, in relation to healthy elderly [17–20].

3.3

Summary

• The pineal gland exerts its effect on human physiology through a variety of functions such as an endocrine gland, hormonal regulation, and circadian rhythm. • In the last 40 years, advances have been made in the compression of pineal physiology mainly on its functions in the circadian rhythm, sleep, and temperature regulation. • New advances in the physiology of the pineal gland are the molecular description of melatonin receptors. • Most of the information that exists on the physiology of the PG is limited to the effects of melatonin and the exclusion of other indoles and pineal peptides (see Fig. 3.1). Questions on Physiology of the Pineal Gland 1. Which of the following is false? A. PG secretes mainly melatonin. B. Melatonin secretion is related to light changes. C. The pinealocyte activates in the light phase to secrete melatonin.

3  Physiology of the Pineal Gland

27 MAMMALIAN PINEAL

INPUT

Locomotor Activity

Sympathic Pineal Innervation

Hypothalamic hormones

LH-RH TSH-RH M/F

Neurohormonal Pituitary hormones

FSH LH Protactin MSH

Hornonal Sex Steroids

Androgens Estrogens Progesterone

Indoleamines and Polypeptides

Sleeping Habenulo-Pineal Innervation

Smell

PINEAL GALND

Neural

Light/Dark Sound Temperature Underfeeding Locomotor Activity Sleeping

OUTPUT

Parvocell. Neuroserc. syst. Hypothalamus

Pituitary

FSH LH TSH ACTH Prolactin Somatostatin MSH

FSH-RH LH-RH TSH-RH C-RH PI/RF SI/RF M/F

Targets

Parathyroid

Sex Organs Thyroid Adrenals Mamma Growth Pigmentatio

Sex Steriods Thyroid Hormones Epinephrine Corticosteriods

Parathyroid Hormones

Thyroid Hormones Pancreas Neurohumoral

Vasopressin Oxytocin Magnocell Neuroserc. syst.

Non-pineal Indoleamines and Catecholamines

Islet Hormones

Fig. 3.1  Hormonal functions of the mammalian pineal gland

D. The physiological significance of PG function other than melatonin has not fully understood yet. E. PG has no exocrine function. 2 . Which of the following is true? A. The primary step of melatonin synthesis involves the conversion of serotonin to N-acetyl serotonin. B. The last step of melatonin synthesis is methylation. C. The phosphorylated form of arylalkylamine N-acetyl-phosphorylase has a major role in the formation of melatonin. D. AN-acetyl-phosphorylase enzyme phosphorylation is mediated by the sympathetic stimulation. E. All of the above. 3. Which of the following is false? A. Melatonin receptors can be found in the cardiac ventricles. B. In the gastrointestinal system, melatonin receptors are found most frequently in the colonic mucosa. C. There are three different melatonin membrane receptors. D. Melatonin receptor type 1b is encoded in the human chromosome 4. E. Melatonin receptor type 1c is not found in human.

28

A. R. Narváez-Rojas et al.

4. Which of the following is true? A. Melatonin has an antioxidant effect. B. Tubulin protein is responsible for the immunomodulatory effects of melatonin. C. Calmodulin is a secondary extracellular messenger. D. The family of hormone receptors related to the retinoid are responsible for production of IL-8. E. Melatonin directly antagonizes the binding of magnesium to calmodulin. 5. Which of the following is false? A. The duration of the melatonin secretory episode transmits information of the diurnal duration. B. Individuals living in northern latitudes show melatonin elongation with peaks during winter nights. C. The rhythmic secretion of melatonin by the PG is the best description of the circadian clock. D. Clock genes are regulated transcriptionally, translationally, and post-­ translationally by self-regulating feedback loops. E. Melatonin is useful to stabilize the sleep cycle. 6. Which of the following is true? A. Melatonin is secreted at daytime. B. Melatonin reduces blood pressure. C. Melatonin induces precocious puberty. D. Melatonin has an exaggeration effect to pain. E. Melatonin affects the memory by direct relation to the thalamus. 7. Which of the following is false? A. The ascent of melatonin in the afternoon around 2 h before going to bed is believed to act as blocking mechanism for sleep onset. B. Low levels of melatonin during the night could be the cause of primary insomnia. C. The production of melatonin is concomitant with aging. D. Melatonin has an effect on both core and skin temperature. E. A causal relationship between the onset of puberty and the decrease in pineal melatonin at this stage has been suggested. 8. Which of the following is true? A. Decreased levels of melatonin may be present in women with hypothalamic hypogonadism. B. Induction of sperm motility in normal semen has been observed after melatonin administration. C. Low melatonin during the night could be the cause of secondary insomnia. D. Melatonin promotes cell division. E. The increase in melatonin production has been associated with fibromyalgia.

3  Physiology of the Pineal Gland

29

Answers 1. C. 2. E. 3. D. 4. A. 5. E. 6. B. 7. C. 8. D.

References 1. Sugden D.  Melatonin biosynthesis in the mammalian pineal gland. Experientia. 1989;45(10):922–32. 2. Arendt J.  Melatonin: characteristics, concerns, and prospects. J Biol Rhythm. 2005;20(4):291–303. 3. Benitez-King G, Anton-Tay F.  Calmodulin mediates melatonin cytoskeletal effects. Experientia. 1993;49(8):635–41. 4. Emet M, Ozcan H, Ozel L, Yayla M, Halici Z, Hacimuftuoglu A. A review of melatonin, its receptors and drugs. Eurasian J Med. 2016;48(2):135. 5. Pévet P. Melatonin receptors as therapeutic targets in the suprachiasmatic nucleus. Expert Opin Ther Targets. 2016;20(10):1209–18. 6. Al-Ghoul WM, Herman MD, Dubocovich ML.  Melatonin receptor subtype expression in human cerebellum. Neuroreport. 1998;9(18):4063–8. 7. Bergiannaki JD, Soldatos CR, Paparrigopoulos TJ, Syrengelas M, Stefanis CN. Low and high melatonin excretors among healthy individuals. J Pineal Res. 1995;18(3):159–64. 8. James O. In: Olcese J, editor. Melatonin after four decades. Boston, MA: Springer; 2002. 9. Pangerl B, Pangerl A, Reiter RJ. Circadian variations of adrenergic receptors in the mammalian pineal gland: a review. J Neural Transm. 1990;81(1):17–29. 10. Borjigin J, Wang MM, Snyder SH.  Diurnal variation in mRNA encoding serotonin N-acetyltransferase in pineal gland. Nature. 1995;378(6559):783. 11. Burgess HJ, Trinder J, Kim Y, Luke D. Sleep and circadian influences on cardiac autonomic nervous system activity. Am J Phys Heart Circ Phys. 1997;273(4):H1761–8. 12. Attanasio A, Borrelli P, Gupta D. Circadian rhythms in serum melatonin from infancy to adolescence. J Clin Endocrinol Metab. 1985;61(2):388–90. 13. Blask DE, Lemus-Wilson AM, Wilson ST.  Breast cancer: a model system for studying the neuroendocrine role of pineal melatonin in oncology. Biochem Soc Trans. 1992;20(2):309–11. 14. Reiter RJ, Rosales-Corral SA, Tan DX, Acuna-Castroviejo D, Qin L, Yang SF, Xu K. Melatonin, a full service anti-cancer agent: inhibition of initiation, progression and metastasis. Int J Mol Sci. 2017;18(4):843. 15. Haimov I, Laudon M, Zisapel N, Souroujon M, Nof D, Shlitner A, Herer P, Tzischinsky O, Lavie P. Sleep disorders and melatonin rhythms in elderly people. BMJ. 1994;309(6948):167. 16. Dawson D, Encel N. Melatonin and sleep in humans. J Pineal Res. 1993;15(1):1–2. 17. Laudon M, Frydman-Marom A. Therapeutic effects of melatonin receptor agonists on sleep and comorbid disorders. Int J Mol Sci. 2014;15(9):15924–50. 18. Berga SL, Mortola JF, Yen SS. Amplification of nocturnal melatonin secretion in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab. 1988;66(1):242–4. 19. Arendt J, Skene DJ, Middleton B, Lockley SW, Deacon S. Efficacy of melatonin treatment in jet lag, shift work, and blindness. J Biol Rhythm. 1997;12(6):604–17. 20. Pacchierotti C, Iapichino S, Bossini L, Pieraccini F, Castrogiovanni P. Melatonin in psychiatric disorders: a review on the melatonin involvement in psychiatry. Front Neuroendocrinol. 2001;22(1):18–32.

4

Neuroimaging of the Pineal Gland Hernando Alvis-Miranda, Kalil Kafury-Benedetti, Osvaldo Molina-Olier, Fernando Ponce-Iglesias, and Mustafa Adnan Shamkhi

4.1

Introduction

• Pineal gland is a neuroendocrine organ that influences circadian rhythm and sleep by the secretion of melatonin [1]. • It is one of the circumventricular organs [2]: –– Anatomically, a rounded or crescent-shaped structure like a pine cone –– Attached by the stalk to the diencephalon and the stalk lines the pineal recess whose inferior lip links the pineal gland to the posterior commissure and the superior lip to the habenular commissure (Fig. 4.1) –– Lacks blood-brain-barrier (BBB)

4.2

Imaging Modalities

• MRI is the imaging modality of choice. • Findings can range from innocuous cysts to extensive and aggressive infiltrative lesions. • These lesions may not only affect the pineal region but also can extend to nearby structures and cause compression and/or displacement.

H. Alvis-Miranda (*) Department of Neurosurgery, University of Cartagena, Colombian Foundation Center for Epilepsy and Neurological Diseases—FIRE, Cartagena, Colombia K. Kafury-Benedetti · O. Molina-Olier · F. Ponce-Iglesias Colombian Foundation Center for Epilepsy and Neurological Diseases—FIRE, Cartagena, Colombia M. Adnan Shamkhi Department of Neurosurgery, Neurosurgery Teaching Hospital, Baghdad, Iraq © Springer Nature Switzerland AG 2020 S. S. Hoz et al. (eds.), Pineal Neurosurgery, https://doi.org/10.1007/978-3-030-53191-1_4

31

32

H. Alvis-Miranda et al.

Fig. 4.1  Normal anatomy of the pineal gland and surrounding structures on MRI: (a) splenium of the corpus callosum, (b) pineal gland, (c) tectal plate, (d) mesencephalon, (e) posterior commissure (© courtesy of Colombian Foundation center for epilepsy and neurological diseases FIRE, Cartagena, Colombia)

a

b

c

d e

• Recent advances in MRI such as the development of new sequences like gradient echo (GRE), diffusion-weighted imaging (DWI), perfusion imaging, and spectroscopy have helped to further evaluate pineal gland pathologies. –– Susceptibility-weighted imaging (SWI) [3]: Detect and differentiate intracranial hemorrhage from calcifications. Visualize intracranial vessels. Identify intracranial thromboembolism. –– DWI is used routinely for the evaluation of brain tumors to distinguish hypercellular from hypocellular tumor [4, 5]. –– Perfusion imaging can be acquired with or without intravenous contrast. In the latter, arterial spin labeling can be used [6, 7]. –– On MR spectroscopy (MRS), the metabolic profile, including differences in key metabolites such as NAA, choline, and myoinositol, and the presence of lipids and lactate help to evaluate the differential diagnosis for PRT [8, 9]. • The functional status of the gland has also been evaluated with morphometric MRI parameters: –– The pineal parenchyma volume is positively correlated with 6-­sulfatoxymelatonin levels (i.e., the primary melatonin metabolite). –– Levels of 6-sulfatoxymelatonin does not differ significantly by presence of cysts or calcification [10]. –– Other abnormal states such as neurodegenerative diseases have been linked with reduced pineal volume, for example, Alzheimer disease [10]. • For evaluation of midline structures and abnormalities, conventional sequences should be acquired in multiple planes. • Only vascular structures and areas of the brain that have no BBB (choroid plexus, pineal and anterior lobe of pituitary gland) physiologically enhance after contrast injection [10–12].

4  Neuroimaging of the Pineal Gland

4.3

33

Nonneoplastic Pineal Findings

4.3.1 Pineal Calcifications • As in the choroid plexus, habenula, and dura mater, calcifications of the pineal gland can be found incidentally on brain imaging. • Pineal calcifications are mainly associated with brain aging (Fig. 4.2). • Around 70% of population have pineal calcifications, predominantly in males [13]. • Various pathological entities, such as intracerebral hemorrhage, stroke, and schizophrenia, have been recently linked to pineal calcification [14, 15]. • Frank or multiple pineal calcifications in children 2 mm –– Hemorrhage into the cyst –– Complications arising from the cyst: Compression of the tectal plate Aqueductal narrowing causing hydrocephalus • For additional information, see Chap. 6.

4.3.3 Vascular Abnormalities • Pineal vascular malformations are very rare [21]. • Arteriovenous malformations (AVMs) are mainly fed by lateral posterior choroidal arteries and draining into the vein of Galen (VOG).

4  Neuroimaging of the Pineal Gland

35

• Recognizing the existence of a pineal gland AVM is important. • Intraparenchymal pineal AVMs should be distinguished from AVMs of other deep-seated locations (e.g., midbrain) and from the grouping of heterogeneous AVMs that make up so-called pineal region AVMs [21].

4.4

Pineal Tumors

4.4.1 Pineal Parenchymal Tumors (PPT) • PPT represent approximately 15–30% of all pineal region masses. • These tumors include: –– Pineocytomas –– Pineal parenchymal tumors of intermediate differentiation (PPTID) –– Pineoblastomas • There is a lack in the medical literature regarding the perfusion and diffusion findings in PPT. • MRI techniques can be applied to help differentiate between grade II and III tumors (Table 4.1). –– Increased perfusion with restricted diffusion and low ADC values in grade III tumors [7].

4.4.1.1 Pineocytoma • The most benign histological type of PPT. • They are nearly indistinguishable histologically from normal parenchyma. • Constitute approximately 14–30% of all PPT. • Predominates in adults between third to sixth decades. • On CT, they could appear as iso- or hypodense mass with heterogeneous enhancement with contrast. • On MRI, they can appear as T2 hyperintense round or lobular lesions with peripheral “exploded” calcifications, cystic changes, and in some cases a hemorrhagic component. Additionally, they strongly enhance on contrast. 4.4.1.2 Pineal Parenchymal Tumor of Intermediate Differentiation (PPTID) • A relatively recently described tumor entity. • There are no pathognomonic features on neuroimaging for PPTID. • It is believed that PPTID may account for at least 20% of all PPT [22]. • On NECT, they show the classic peripheral “exploded” calcifications and bulky, aggressive mass with local brain invasion [22]. • On MRI, post-contrast scans showed marked heterogeneous enhancement with some cystic foci [22–24]. • Komakula et al. [22] recommended a higher index of suspicion of PPTID when: –– PPT are larger than normal –– There is local invasion –– They are more heterogeneous than PCs

35–40 years

Middle-Aged, older patients

Pineocytoma

PPTID

round or lobular mass Lobulated

lobulated Restriction in cyst-solid, single solid (high cyst, lobulated cellular) parts cysts, or lobulated solid mass

Rare usually older Heterogenous with invasive potential

MRI T1 T2

Densities of calcium, soft tissue, cysts, and fat Iso- to Hypointense hyperintense (fat) (calcium)

Isointense small, intratumor, hyperintense, cystic-appearing foci Mixed density; Heterogeneous; Heterogeneous— solid portion solid portion iso-/ Solid portion iso-/ frequently hypointense hypointense more hyperdense common than minimally hyperintense to cortex—Frequent necrosis/ hemorrhage, cysts Iso-/hypodense heterogeneously Heterogeneously hyperintense iso-/hyperintense Hyperdense Iso-/hyperintense Iso- to hyperintense

Hyperintense

FLAIR

—

Heterogeneous Heterogehypointensities, neous with or without mild perilesional edema

Iso-/hyperintense Engulfed

Hyperintense

Less frequent

Frequent

—

Frequent

Less common Less common

Moderate heterogeneous Strong, homogeneous ± CSF seeding ± brain invasion Marked enhancement in solid portion of the lesion

Heterogeneous

Avid, solid or peripheral Avid, heterogeneous

Calcification Hemorrhage Enhancement Peripheral exploded Engulfed

Mild peritumoral Peripheral edema characteristic

± Hyperintense

Hyperintense

—

↑ Choline, ↓ NAA, ± lactate

—

↑ Cho, ↓ NAA Prominent glutamate and taurine peak

Elevated Cho, decreased NAA, lactate doublet.

Spectroscopy

PPTID pineal parenchymal tumor of intermediate differentiation, PTPR papillary tumors of the pineal region, NAA N-acetyl-aspartate, Cho choline, CSF cerebrospinal fluid, M male, F female

Teratoma

Germinoma

PTPR

CT

Round or lobular Iso-/hypodense Iso- to mass hypointense lobulated mass Hyperdense Mixed iso-/ hypointense

Morphology

Pineoblastoma Most common in Irregular mass children but can occur at any age M = F CSF spread common

Clinical data

Tumor

Table 4.1  Summary of clinical and imaging features of pineal tumors

36 H. Alvis-Miranda et al.

4  Neuroimaging of the Pineal Gland

37

4.4.1.3 Pineoblastoma • Pineoblastomas (PNB) are malignant, high-grade (WHO grade IV), undifferentiated, embryonal tumors. • They are categorized as primitive neuroectodermal tumors (PNET) representing at least 40% of PPT. • Frequently associated with CSF dissemination and infiltration to adjacent structures. • They can occur in isolation, but also in association with retinoblastoma (i.e., trilateral retinoblastoma). • PNB are commonly seen in children 7mm

NO

hydrocephalus or Parinaud?

nonspecific symptoms?

YES

NO

YES extensive workup to rule out other causes

periodical clinical and MR follow-up

YES

consider surgery

worsening or severe symptoms?

NO

observation

Fig. 6.2  Management flow chart of Pineal cyst (© Courtesy of Prof. Vladimír Beneš, Department of Neurosurgery and Neurooncology, First Faculty of Medicine of Charles University, Military University Hospital Prague, Czech Republic)

• Explanation of benign nature of PC to the patient is important. Sometimes reassurance that PC is not “ticking bomb inside the head” may improve presenting symptoms. • Some authors perform routine annual MRI scanning and a clinical examination in asymptomatic patients [20]. • Others do not recommend periodical follow-up in an asymptomatic adult patient if a cyst looks typical on MRI [8, 12, 35].

82

M. Majovsky

6.1.7.2 Symptomatic Treatment • Symptomatic treatment consists of pain management, supportive psychotherapy, and implementation of sleep hygiene measures. Close cooperation of neurosurgeon, neurologist, neuropsychologist, and endocrinologist is essential. • One case report of a successful melatonin substitution in the treatment of intractable headache has been published [36]. 6.1.7.3 Surgical Treatment A. General • Patients with obstructive hydrocephalus have a straightforward indication for surgery. In an acute setting, an external ventricular drainage can be placed as the first step [37]. Restoration of a physiological circulation of the cerebrospinal fluid by PC removal is the goal, and the improvement in these patients is usually excellent. • The surgical treatment of patients with PCs presenting with non-specific symptoms is possible, but highly controversial within the neurosurgical community.9 • In patients with non-specific symptoms, an extensive workup, including neurological, psychological, and endocrinological examination, is needed to rule out all other possible causes. • In the differential diagnosis, primary headache, cervical disc disease, Meniere disease, benign paroxysmal positional vertigo, or pituitary adenoma should be considered. Many of the symptoms may be psychogenic as a part of a somatoform disorder. It is a challenge to differentiate between somatic symptoms and somatization. People with chronic pain and sleep disturbances often have psychological problems and vice versa [40]. • After a serious consideration, surgery can be offered to a subset of patients with severe non-specific symptoms as a last-tier therapy.10 • Surgery might also be considered in atypical cases in which the histological diagnosis is uncertain. Especially in cases of multilobular PCs or heterogeneous contrast enhancement that is suspicious of a tumor. Several cases have been described in the literature in which pineal tumor was misdiagnosed as PCs [25, 41]. • If surgical treatment of PCs was considered, modern neurosurgery offers multiple surgical options such as microsurgery, endoscopy, and stereotaxy.

9  An online survey was conducted to analyze clinical management of patients with PC among neurosurgeons worldwide [42]. Most of respondents have operated on patients with a PC only if they presented with symptoms attributable to a mass effect. Surgery for patients with non-specific complaints is not widely accepted (only 15% respondents do so), although some agree that such surgery may be effective. 10  Large surgical series report the proportion of operated patients to be 16.6–20.9% [20, 31, 43, 44]. Obviously, these numbers are high due to selection bias. The real proportion of patients with PC in the general population who might benefit from the surgery is much smaller.

6  Non-tumorous Lesions of the Pineal Gland

83

B. Microsurgery • In most cases the goal of surgery is PC resection, which is achieved microsurgically either by a supracerebellar infratentorial (SCIT) or an occipital transtentorial approach (OTT). • The SCIT approach is a straightforward technique via a natural corridor between the superior aspect of the cerebellum and the tentorium (see Chap. 7). This approach is favored by most neurosurgeons [42]. Preferably, the unilateral SCIT approach is used to protect a dominant transverse sinus and spare some bridging veins between the cerebellum and the tentorium that are in the surgical corridor. A radical PC resection is achievable in almost all cases. Possible complications include diplopia and venous infarction of the cerebellum.11 • Another common microsurgical approach is OTT. In contrast to SCIT, the pineal region is accessed supratentorially along the falcotentorial angle. A slight retraction of the occipital lobe and incision of the tentorial apex are necessary to create a surgical corridor toward the PC. The most common complication after OTT is hemianopia.12 • Microsurgery shows the highest rate of clinical improvement, with more than 90% showing improvement [20, 32, 43, 44]. • The matter of physiological changes after radical PC resection is not yet fully resolved.13 C. Stereotactic Surgery • A stereotactic approach enables puncture and an aspiration of the PC and may serve as a biopsy as well. • Improvement rate might be lower and recurrence rate higher when compared to microsurgical resection.14 D. Endoscopy • Main advantage of endoscopic transventricular approach is possibility to address both PC and coexisting hydrocephalus by performing a third ventriculostomy.

 In the largest surgical series, all patients underwent surgery of PC using the SCIT approach in a sitting position. In this patient group, the complication rate was 0% [32]. 12  Hemianopia occurs transiently after OTT approach in 16.1–79% of the patients and permanently in 0–4.1% [37, 45, 46]. Berhouma et al. used OTT in 20 patients with PC and achieved radical resection of PCs in 70% with a complication rate of 20% (four patients with transient hemianopia) [37]. 13  Majovsky et al. examined melatonin and cortisol secretion profiles in four patients before and after PC resection. In all cases patients experienced a loss of endogenous pineal melatonin production, which equated with pinealectomy. Surprisingly, cortisol secretion substantially increased in patients after surgery [30]. 14  Kreth et al. reported the largest case series using stereotactic aspiration of PCs (n = 14 patients). The authors encountered no complications, but clinical improvement was achieved in only 42.9% of the patients. No recurrence was noted in this series, although Mena et al. reported the regrowth of a PC in their series with only one patient treated with stereotactic aspiration [51]. Stern and Ross treated two patients with PC using stereotactic aspiration and one of the PC regrew in 6 years [52].

11

84

M. Majovsky

• Complete removal of a PC is usually not possible. • Risk of recurrence might be higher when compared to the microsurgical removal of PC.15 E. Results of Surgical Treatment • The literature reports overall clinical improvement ranging between 42.9% and 100%. Recent studies have shown a clinical improvement of over 90% [41]. • Improvement in symptoms of increased intracerebral pressure due to hydrocephalus or oculomotor palsy caused by the direct compression of mesencephalon reaches 100% when the mass effect of PC is removed. With total resection of PC, there was no regrowth [41]. • Some studies suggest superiority of total or near-total PC resection over fenestration in terms of clinical outcome (i.e., higher symptoms relief).16 • In patients with headache as the only complaint, surgery is curative in 25–100% [29, 31, 32, 43, 44, 47, 48]. Other non-specific symptoms have not specifically been examined. • Even an unusual, rare presentation of PC (such as seizures, mono-paresthesia, face numbness, tremor, ataxia, hemiparesis, or syncope) could resolve after PC resection [29, 32, 48–50]. • The exact mechanism of relief of non-specific symptoms is not easily explained by PC resection; instead, some might argue for the suspicion of a placebo effect [53].

6.2

Pineal Apoplexy

• Apoplexy of pineal gland is bleeding into or impaired blood supply of the pineal gland. • It is a rare diagnosis; literature contains only several tens of cases. • Pineal apoplexy shares some similarities with pituitary apoplexy due to the similar anatomy and blood supply of both glands [13]. • Apoplexy may occur in the presence of tumor, PC, or adjacent cavernoma.17 It may be facilitated by anticoagulation therapy [13, 54–57].  Tirakotai et al. performed an endoscopic fenestration and biopsy in nine patients. No complications occurred in this series but one PC recurred. Regrettably, the authors do not state the clinical outcome of the patients. 16  Eide et al. reported on 21 operated patients: 15 had their PC resected and 6 had their PC microscopically fenestrated. The authors found significantly better results in the resection group [44]. Majovsky et al., in their series of patients with PC resection, spared some pineal tissue (less than half of the PC) to prevent total melatonin secretion loss [20]. Despite this sparing strategy, authors still achieved improvement in 95.2% of patients. 17  Mattogno et  al. described two cases of vanishing pineal tumor following apoplexy [13]. This phenomenon has been described in pituitary apoplexy as well. McNeely et al. speculate that bleeding into the pineal gland may promote PC formation [18]. 15

6  Non-tumorous Lesions of the Pineal Gland

a

85

b

Fig. 6.3  T2-weighted images MRI, axial view (a) and sagittal view (b), show fluid-fluid level of pineal apoplexy (red arrow) (© Courtesy of Prof. Vladimír Beneš, Department of Neurosurgery and Neurooncology, First Faculty of Medicine of Charles University, Military University Hospital, Prague, Czech Republic)

• Typical clinical presentation is sudden onset or acute worsening of following symptoms: headache, gaze paresis, nausea/vomiting, syncope, and ataxia [17, 58]. In certain cases, acute bleeding into pineal gland may cause rapid increase in size and acute hydrocephalus, which is a surgical emergency. Cases of sudden death due to pineal apoplexy have been described [59]. • Diagnosis is usually based on sudden onset of symptoms and confirmed by CT and MRI, sometimes with visible fluid-fluid level inside PC on axial slice representing blood [57]. Few cases of subarachnoid hemorrhage caused by pineal apoplexy have been reported [60] (Fig. 6.3). • Treatment of mild cases of pineal apoplexy is primarily symptomatic, i.e., pain management, administration of antiemetic drugs, and physical therapy. • In acute presentation (e.g., hydrocephalus), patient is admitted to intensive care unit with placement of external ventricular drain. Goal of surgical treatment is restoration of physiologic cerebrospinal fluid pathways by resection of ­hemorrhagic gland. Alternatively, one can consider third ventriculostomy or ventriculoperitoneal shunt placement.

6.3

Calcifications

• The pineal gland has a predilection for calcification which is invariably histologically present in adults (acervulus cerebri, corpora arenacea) [63]. • Calcifications in pineal gland are often seen on plain skull radiogram and are considered normal.

86

M. Majovsky

• In CT series, prevalence reaches 60% in third decade and 90% in ninth decade [64]. • In children under the age of 10 years, pineal calcification is unusual and might be suggestive of presence of a neoplasm, such as germinoma or teratoma [65]. • Some authors found association between pineal gland calcification and certain pathological conditions in adults such as tumors or strokes [66–68], while others dispute this association [69].

6.4

Other Non-tumorous Pathologies of Pineal Gland

• Arteriovenous malformation (AVM) of pineal gland has been described in case reports.18 • Abscess may rarely form in the pineal gland or in preformed PC. Spread of infectious agent is either hematogenous or per continuitatem.19 • Many other pathologies might occur in the close vicinity of pineal gland—in the pineal region. These pathologies include tumors (metastasis, meningiomas, hemangioblastomas, neuroectodermal tumors, or lipomas), non-tumorous lesions (arachnoid cyst, lipoma), and vascular lesions (cavernomas, arteriovenous malformations, vein of Galen malformations). Clinical presentation is somehow non-specific and very similar to the clinical presentation of pineal gland tumors (see Chap. 5).

6.5

Summary

• PC is a benign cystic lesion of pineal gland. • Prevalence in general population is 0.7–1.5%. • The best diagnostic tool is MRI. “Typical” MRI appearance of a PC is a smooth-­ walled cystic lesion in the pineal region with rim enhancement. • Most PCs are asymptomatic, and their diagnosis is rather incidental. • Observation is indicated in most cases. • Hydrocephalus and Parinaud’s syndrome are absolute indications for surgery. • Surgical treatment in patients with non-specific symptoms is controversial. However, literature suggests improvement in majority of patients.

 Weil et al. reported case of intraparenchymal pineal AVM. Patient presented with intraventricular hemorrhage and hydrocephalus. AVM was fed by posterior choroidal arteries and draining into an ectatic vein of Galen. Diagnosis was confirmed on histopathological examination following successful surgical removal [61]. 19  Ko et al. reported case of delayed abscess in patient after transsphenoidal resection of pituitary adenoma associated with cerebrospinal fluid leak [62]. 18

6  Non-tumorous Lesions of the Pineal Gland

87

Questions on Non-tumorous Lesions of the Pineal Gland 1. Etiology of pineal cysts may include: A. Brain hypoxia in the perinatal period. B. Pineal necrosis. C. Sequestration of the pineal recess. D. Exact pathogenesis is unknown. E. All of the above. 2. The usual appearance of pineal cyst on CT scan: A. Irregular shape with heterogeneous enhancement, with no calcification. B. Well-circumscribed lesion with a thin rim of enhancement; calcification is possible. C. Regular shape with homogenous enhancement, no calcification. D. Irregular shape with homogenous enhancement; calcification is possible. E. None of the above. 3. The best MRI view and sequence help to assess pineal cyst is: A. T1 coronal B. T1 sagittal C. T2 sagittal D. T2 axial E. T2 axial 4. “Typical” MRI appearance of a pineal cyst is: A. Well circumscribed with no enhancement B. Irregular shape with homogenous enhancement C. Irregular shape with heterogeneous enhancement D. A smooth-walled cyst with rim enhancement E. None of the above 5. Histologically, pineal cyst might be mistaken for: A. Meningioma B. Pineoblastoma C. Teratoma D. Germinoma E. Pineocytoma 6. Clinically, most patients with pineal cyst present with: A. Acute hydrocephalus B. Asymptomatic C. Parinaud’s syndrome D. Vertigo E. Tremor 7. Seizures very rarely occur with pineal cyst; a possible explanation could be: A. Compression on temporal lobe B. Disturbance of noradrenaline centrally C. Disturbance of noradrenaline peripherally D. Melatonin disturbance or compression of the vein of Galen E. None of the above

88

M. Majovsky

8. The usual treatment of pineal cyst is: A. Surgical B. Radiotherapy C. Chemotherapy D. Observation E. Steroids 9. In pineal cyst, surgery is indicated when there is: A. Headache B. Paroxysmal positional vertigo C. Hyperprolactinemia D. Seizure E. Obstructive hydrocephalus 10. Surgical treatment of pineal cyst (PC); all are true except: A. Microsurgery has the highest rate of clinical improvement. B. In microsurgery, a radical PC resection is achievable in almost all cases. C. In stereotactic approach, improvement rate might be lower and recurrence rate higher when compared to microsurgery. D. Endoscopically complete removal of the cyst is usually possible. E. Main advantage of endoscopic approach is the possibility to address both PC and coexisting hydrocephalus. 11. In pineal cysts (PCs), all are true except: A. Most PCs are asymptomatic. B. PC wall consists of three layers, namely, glial, pineal, and collagenous. C. In cases of atypical MRI appearance, surgery might be justified to obtain tissue sample. D. A rim of gadolinium enhancement usually exceeds 2 mm of thickness. E. A stereotactic approach enables puncture and an aspiration of the PC and may serve as a biopsy as well. 12. Concerning pineal apoplexy, all are true except: A. It is a rare diagnosis. B. Shares some similarities with pituitary apoplexy. C. Can cause sudden death. D. It may be facilitated by anticoagulation therapy. E. Blood leakage into the subarachnoid space never occurs because the gland lacks a blood-brain barrier. 13. Concerning pineal gland calcifications, all are true except: A. PG has a predilection for calcification. B. In CT series, prevalence reaches 60% in third decade and 90% in ninth decade. C. In children under the age of 10 years pineal calcification is usual. D. Presence of calcification in children might be suggestive of a neoplasm. E. Often seen on plain skull radiogram and are considered normal.

6  Non-tumorous Lesions of the Pineal Gland

89

Answers 1. E. 2. B. 3. C. 4. D. 5. E. 6. B. 7. D. 8. D. 9. E. 10. D. 11. D. 12. E. 13. C. Acknowledgment  I would like to acknowledge prof. Vladimir Benes, M.D., Ph.D. for his support and valuable help during the preparation of this chapter.

References 1. Virchow RL.  Die krankhaften Geschwülste: dressig Volesungen gehalted während des Wintersemesters 1862–1863 an der Universität zu Berlin. A. Hirschwald; 1865. 2. Campbell AW.  Notes of two cases of dilatation of central cavity or ventricle of the pineal gland. Trans Pathol Soc (Lond). 1899;50:15–8. 3. Pussep L.  Die operative Entfernung einer Zyste der Glandula pinealis. Neurol Zentralbl. 1914;33:560–3. 4. Liber AF. Cystic hydrops of the pineal gland. J Nerv Ment Dis. 1939;89(6):782–94. 5. Nolte I, Brockmann MA, Gerigk L, Groden C, Scharf J. TrueFISP imaging of the pineal gland: more cysts and more abnormalities. Clin Neurol Neurosurg. 2010;112(3):204–8. 6. Tapp E, Huxley M. The histological appearance of the human pineal gland from puberty to old age. J Pathol. 1972;108(2):137–44. 7. Hasegawa A, Ohtsubo K, Mori W. Pineal gland in old age; quantitative and qualitative morphological study of 168 human autopsy cases. Brain Res. 1987;409(2):343–9. 8. Al-Holou WN, Terman SW, Kilburg C, Garton HJ, Muraszko KM, Chandler WF, Ibrahim M, Maher CO.  Prevalence and natural history of pineal cysts in adults. J Neurosurg. 2011;115(6):1106–14. 9. Sawamura Y, Ikeda J, Ozawa M, Minoshima Y, Saito H, Abe H. Magnetic resonance images reveal a high incidence of asymptomatic pineal cysts in young women. Neurosurgery. 1995;37(1):11–6. 10. Golzarian J, Balériaux D, Bank WO, Matos C, Flament-Durand J. Pineal cyst: normal or pathological? Neuroradiology. 1993;35(4):251–3. 11. Barboriak DP, Lee L, Provenzale JM.  Serial MR imaging of pineal cysts: implications for natural history and follow-up. Am J Roentgenol. 2001;176(3):737–43. 12. Nevins EJ, Das K, Bhojak M, Pinto RS, Hoque MN, Jenkinson MD, Chavredakis E. Incidental pineal cysts: is surveillance necessary? World Neurosurg. 2016;90:96–102. 13. Mattogno PP, Frassanito P, Massimi L, Tamburrini G, Novello M, Lauriola L, Caldarelli M.  Spontaneous regression of pineal lesions: ghost tumor or pineal apoplexy? World Neurosurg. 2016;88:64–9.

90

M. Majovsky

14. Al-Holou WN, Maher CO, Muraszko KM, Garton HJ. The natural history of pineal cysts in children and young adults. J Neurosurg Pediatr. 2010;5(2):162–6. 15. Bregant T, Rados M, Derganc M, Neubauer D, Kostovic I. Pineal cysts-a benign consequence of mild hypoxia in a nearterm brain. Neuro Endocrinol Lett. 2011;32:663–6. 16. Özmen E, Derinkuyu B, Samancı C, Ünlü HA, Demirkan TH, Haşıloğlu ZI, Kuruoğlu S, Adaletli İ. The prevalence of pineal cyst in patients with cerebral palsy. Diagn Interv Radiol. 2015;21(3):262. 17. Koenigsberg RA, Faro S, Marino R, Turz A, Goldman W. Imaging of pineal apoplexy. Clin Imaging. 1996;20(2):91–4. 18. McNeely PD, Howes WJ, Mehta V. Pineal apoplexy: is it a facilitator for the development of pineal cysts? Can J Neurol Sci. 2003;30(1):67–71. 19. Cooper ER. The human pineal gland and pineal cysts. J Anat. 1932;67(Pt 1):28. 20. Májovský M, Netuka D, Beneš V. Conservative and surgical treatment of patients with pineal cysts: prospective case series of 110 patients. World Neurosurg. 2017;105:199–205. 21. Osborn AG, Preece MT.  Intracranial cysts: radiologic-pathologic correlation and imaging approach. Radiology. 2006;239(3):650–64. 22. Inoue Y, Saiwai S, Miyamoto T, Katsuyama J. Enhanced high-resolution sagittal MRI of normal pineal glands. J Comput Assist Tomogr. 1994;18(2):182–6. 23. Pastel DA, Mamourian AC, Duhaime AC. Internal structure in pineal cysts on high-resolution magnetic resonance imaging: not a sign of malignancy. J Neurosurg Pediatr. 2009;4(1):81–4. 24. Fleege MA, Miller GM, Fletcher GP, Fain JS, Scheithauer BW.  Benign glial cysts of the pineal gland: unusual imaging characteristics with histologic correlation. Am J Neuroradiol. 1994;15(1):161–6. 25. Starke RM, Cappuzzo JM, Erickson NJ, Sherman JH.  Pineal cysts and other pineal region malignancies: determining factors predictive of hydrocephalus and malignancy. J Neurosurg. 2017;127(2):249–54. 26. Cauley KA, Linnell GJ, Braff SP, Filippi CG. Serial follow-up MRI of indeterminate cystic lesions of the pineal region: experience at a rural tertiary care referral center. Am J Roentgenol. 2009;193(2):533–7. 27. Taraszewska A, Matyja E, Koszewski W, Zaczyñski A, Bardadin K, Czernicki Z.  Asymptomatic and symptomatic glial cysts of the pineal gland. Folia Neuropathol. 2008;46(3):186–95. 28. Fakhran S, Escott EJ.  Pineocytoma mimicking a pineal cyst on imaging: true diagnostic dilemma or a case of incomplete imaging? Am J Neuroradiol. 2008;29(1):159–63. 29. Fain JS, Tomlinson FH, Scheithauer BW, Parisi JE, Fletcher GP, Kelly PJ, Miller GM. Symptomatic glial cysts of the pineal gland. J Neurosurg. 1994;80(3):454–60. 30. Májovský M, Řezáčová L, Sumová A, Pospíšilová L, Netuka D, Bradáč O, Beneš V. Melatonin and cortisol secretion profile in patients with pineal cyst before and after pineal cyst resection. J Clin Neurosci. 2017;39:155–63. 31. Fetell MR, Bruce JN, Burke AM, Cross DT, Torres RA, Powers JM, Stein BM. Non, neoplastic pineal cysts. Neurology. 1991;41(7):1034. 32. Hajnsek S, Paladino J, Petelin Gadze Z, Nankovic S, Mrak G, Lupret V.  Clinical and neurophysiological changes in patients with pineal region expansions. Coll Antropol. 2013;37(1):35–40. 33. Engel U, Gottschalk S, Niehaus L, Lehmann R, May C, Vogel S, Jänisch W. Cystic lesions of the pineal region–MRI and pathology. Neuroradiology. 2000;42(6):399–402. 34. Seifert CL, Woeller A, Valet M, Zimmer C, Berthele A, Tölle T, Sprenger T. Headaches and pineal cyst: a case–control study. Headache. 2008;48(3):448–52. 35. Jussila MP, Olsén P, Salokorpi N, Suo-Palosaari M. Follow-up of pineal cysts in children: is it necessary? Neuroradiology. 2017;59(12):1265–73. 36. Karadaş Ö, İpekdal İH, Ulaş ÜH, Odabaşi Z. Nocturnal headache associated with melatonin deficiency due to a pineal gland cyst. J Clin Neurosci. 2012;19(2):330–2. 37. Berhouma M, Ni H, Delabar V, Tahhan N, Salem SM, Mottolese C, Vallee B.  Update on the management of pineal cysts: case series and a review of the literature. Neurochirurgie. 2015;61(2–3):201–7.

6  Non-tumorous Lesions of the Pineal Gland

91

38. Eide PK, Ringstad G. Increased pulsatile intracranial pressure in patients with symptomatic pineal cysts and magnetic resonance imaging biomarkers indicative of central venous hypertension. J Neurol Sci. 2016;367:247–55. 39. Eide PK, Pripp AH, Ringstad GA. Magnetic resonance imaging biomarkers indicate a central venous hypertension syndrome in patients with symptomatic pineal cysts. J Neurol Sci. 2016;363:207–16. 40. Smith MT, Haythornthwaite JA.  How do sleep disturbance and chronic pain inter-relate? Insights from the longitudinal and cognitive-behavioral clinical trials literature. Sleep Med Rev. 2004;8(2):119–32. 41. Májovský M, Netuka D, Beneš V. Is surgery for pineal cysts safe and effective? Short review. Neurosurg Rev. 2018;41(1):119–24. 42. Májovský M, Netuka D, Beneš V. Clinical management of pineal cysts: a worldwide online survey. Acta Neurochir. 2016;158(4):663–9. 43. Kalani MY, Wilson DA, Koechlin NO, Abuhusain HJ, Dlouhy BJ, Gunawardena MP, Nozue-Okada K, Teo C.  Pineal cyst resection in the absence of ventriculomegaly or Parinaud’s syndrome: clinical outcomes and implications for patient selection. J Neurosurg. 2015;123(2):352–6. 44. Eide PK, Ringstad G. Results of surgery in symptomatic non-hydrocephalic pineal cysts: role of magnetic resonance imaging biomarkers indicative of central venous hypertension. Acta Neurochir. 2017;159(2):349–61. 45. Yoshimoto K, Araki Y, Amano T, Matsumoto K, Nakamizo A, Sasaki T. Clinical features and pathophysiological mechanism of the hemianoptic complication after the occipital transtentorial approach. Clin Neurol Neurosurg. 2013;115(8):1250–6. 46. Qi S, Fan J, Zhang XA, Zhang H, Qiu B, Fang L. Radical resection of nongerminomatous pineal region tumors via the occipital transtentorial approach based on arachnoidal consideration: experience on a series of 143 patients. Acta Neurochir. 2014;156(12):2253–62. 47. Michielsen G, Benoit Y, Baert E, Meire F, Caemaert J. Symptomatic pineal cysts: clinical manifestations and management. Acta Neurochir. 2002;144(3):233–42. Discussion 242. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11956936 48. Mandera M, Marcol W, Bierzyńska-Macyszyn G, Kluczewska E. Pineal cysts in childhood. Childs Nerv Syst. 2003;19(10–11):750–5. 49. Menovsky T, De Ridder D, Grotenhuis JA.  Non-specific symptoms related to pineal cysts. Minim Invasive Neurosurg. 2011;54:50. 50. Morgan JT, Scumpia AJ, Webster TM, Mittler MA, Edelman M, Schneider SJ.  Resting tremor secondary to a pineal cyst: case report and review of the literature. Pediatr Neurosurg. 2008;44(3):234–8. 51. Mena H, Armonda RA, Ribas JL, Ondra SL, Rushing EJ. Nonneoplastic pineal cysts: a clinicopathologic study of twenty-one cases. Ann Diagn Pathol. 1997;1(1):11–8. 52. Stern JD, Ross DA.  Stereotactic management of benign pineal region cysts: report of two cases. Neurosurgery. 1993;32(2):310–4. 53. Kulkarni AV. Pineal cyst resection. J Neurosurg. 2015;123(2):350–1. 54. Wang CC, Turner J, Steel T. Spontaneous pineal apoplexy in a pineal parenchymal tumor of intermediate differentiation. Cancer Biol Med. 2013;10(1):43. 55. Kobayashi S, Kamagata M, Nakamura M, Nakazato Y, Sasaki T. Pineal apoplexy due to massive hemorrhage associated with cavernous angioma: case report. Surg Neurol. 2001;55(6):365–71. 56. Tamura Y, Yamada Y, Tucker A, Ukita T, Tsuji M, Miyake H, Kuroiwa T.  Endoscopic surgery for hemorrhagic pineal cyst following antiplatelet therapy: case report. Neurol Med Chir. 2013;53(9):625–9. 57. Sarikaya-Seiwert S, Turowski B, Hänggi D, Janssen G, Steiger HJ, Stummer W. Symptomatic intracystic hemorrhage in pineal cysts: report of 3 cases. J Neurosurg Pediatr. 2009;4(2):130–6. 58. Patel AJ, Fuller GN, Wildrick DM, Sawaya R. Pineal cyst apoplexy: case report and review of the literature. Neurosurgery. 2005;57(5):E1066. 59. Richardson JK, Hirsch CS. Sudden, unexpected death due to “pineal apoplexy”. Am J Forensic Med Pathol. 1986;7(1):64–8.

92

M. Majovsky

60. Mukherjee KK, Banerji D, Sharma R. Pineal cyst presenting with intracystic and subarachnoid haemorrhage: report of a case and review of the literature. Br J Neurosurg. 1999;13(2):189–92. 61. Weil AG, Obaid S, Berthelet F, McLaughlin N, Bojanowski MW. Arteriovenous malformation of the pineal gland. Acta Neurochir. 2012;154(1):65–6. 62. Ko Y, Yi HJ, Kim YS, Oh SH, Kim KM, Oh SJ. Delayed-onset pineal abscess following transsphenoidal surgery for pituitary adenoma: a case report. J Clin Neurosci. 2003;10(5):627–8. 63. Butler P, Mitchell AW, Ellis H, editors. Applied radiological anatomy. Cambridge: Cambridge University Press; 1999. 64. Turgut AT, Karakaş HM, Özsunar Y, Altın L, Çeken K, Alıcıoğlu B, Sönmez İ, Alparslan A, Yürümez B, Çelik T, Kazak E. Age-related changes in the incidence of pineal gland calcification in Turkey: a prospective multicenter CT study. Pathophysiology. 2008;15(1):41–8. 65. Chang CG, Kageyama N, Mobayashi T, Yoshida J, Negoro M. Pineal tumors: clinical diagnosis, with special emphasis on the significance of pineal calcification. Neurosurgery. 1981;8(6):656–68. 66. Tuntapakul S, Kitkhuandee A, Kanpittaya J, Johns J, Johns NP. Pineal calcification is associated with pediatric primary brain tumor. Asia Pac J Clin Oncol. 2016;12(4):e405–10. 67. Kitkhuandee A, Sawanyawisuth K, Johns J, Kanpittaya J, Tuntapakul S, Johns NP.  Pineal calcification is a novel risk factor for symptomatic intracerebral hemorrhage. Clin Neurol Neurosurg. 2014;121:51–4. 68. Kitkhuandee A, Sawanyawisuth K, Johns NP, Kanpittaya J, Johns J. Pineal calcification is associated with symptomatic cerebral infarction. J Stroke Cerebrovasc Dis. 2014;23(2):249–53. 69. Del Brutto OH, Mera RM, Lama J, Zambrano M. Stroke and pineal gland calcification: lack of association. Results from a population-based study (the Atahualpa project). Clin Neurol Neurosurg. 2015;130:91–4.

7

Treatment and Approaches for the Pineal Gland Region Baha’eddin A. Muhsen, Hamid Borghei-Razavi, and Samer S. Hoz

7.1

Introduction

The surgery for pineal region tumors is necessary to obtain a tissue diagnosis as many diverse lesions could arise in this region, and these lesions have no pathognomonic features on neuroimaging. The strategies of surgical intervention for pineal region lesions are: 1. Surgery: primary modality of treatment especially in benign condition has been advanced recently to decrease mortality and morbidity. 2. Biopsy: open microsurgical, endoscopic transventricular, or stereotactic biopsy of lesions are less invasive procedures but infrequently carry the risk of hemorrhage and sampling error. 3. Stereotactic radiosurgery: useful in tumors of the pineal gland of smaller than 3 cm in diameter. It can be used as first line treatment, or it could be utilized as adjuvant therapy. 4. Radiotherapy and chemotherapy: • Germinomas are highly radiosensitive. • High cure rate with craniospinal radiation especially >40  Gy to the local tumor site can be expected.

B. A. Muhsen (*) · H. Borghei-Razavi Department of Neurosurgery, Rose Ella Burkhardt Brain Tumor & Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA e-mail: [email protected]; [email protected] S. S. Hoz Neurosurgery Teaching Hospital, Baghdad, Iraq e-mail: [email protected] © Springer Nature Switzerland AG 2020 S. S. Hoz et al. (eds.), Pineal Neurosurgery, https://doi.org/10.1007/978-3-030-53191-1_7

93

94

B. A. Muhsen et al.

• For disseminated germinomas, craniospinal radiation is the preferred treatment. • For non-disseminated germinomas, most studies support the use of limited field radiotherapy. • A higher radiation dose is recommended in patients with β-hCG germinomas than those with pure germinomas. • Recent trials support giving chemotherapy followed by radiation therapy thus reducing dose and volume for treatment of pure germinomas. • In contrast to germinoma, non-germinomatous germ cell tumors are not treated solely by radiation. • Recent studies suggest the combination of high-dose chemotherapy and high-­ dose craniospinal irradiation for non-germinomatous GCT. • Platinum-based chemotherapy has a success rate over 80% in treatment of germinomas but with 50% relapse after achieving complete response. Hints • The surgical approaches for pineal lesion have evolved, becoming safer and more efficient with the use of microneurosurgery and neuroendoscopy which helped to decrease the mortality and morbidity of surgery. • The anatomy of the region is very complex with many vascular structures beside the variability in the deep venous anatomy and the proximity of dorsal midbrain and other vital structures; thus good preoperative planning must be considered. • The choice of surgical approach must be based on surgeon’s preference as well as the patient’s anatomy. • The goal to reach safest maximum resection while being minimally invasive to avoid complications. • The two most commonly utilized surgical approaches are supracerebellar-­ infratentorial (SCIT) and occipital transtentorial (OTT) approach. Some of the approaches described below have certain indications, and the others were used in the past. New approaches with endoscopy have been evolved but are not yet popularized.

7.2 1. 2. 3. 4. 5. 6. 7. 8. 9.

Surgical Approaches for the Pineal Region (Fig. 7.1)

Supracerebellar-infratentorial (SCIT). Paramedian supracerebellar-infratentorial (lateral SCIT). Occipital transtentorial (OTT) approach. Combined supra-/infratentorial transsinus. Transcortical transventricular approach. Interhemispheric parieto-occipital approach (transcallosal or retrocallosal). Endoscopic transventricular approach. Endoscopic supracerebellar infratentorial approach. Endoscopic-assisted microsurgical approach.

7  Treatment and Approaches for the Pineal Gland Region

95

Fig. 7.1  Surgical approaches for pineal region: (a) endoscopic transventricular, (b) IHPO transcallosal (Dandy) almost abandoned, (c) IHPO retrocallosal, (d) OTT, (e) SCIT (© illustrated by Meleine Landry Konan, Neurosurgeon, University Felix Houphouet Boigny, Ivory Coast)

• The pineal region surgery dates back to 1913 when the first successful operation in the pineal region was reported in Germany, by Hermann Oppenheim who referred a case to Fedor Krause [1, 2]. Supracerebellar infratentorial approach was used. • In 1921, Dandy published a case report of three patients using his Parieto-­ occipital transcallosal approach [1, 3, 4], Walker soon perfected Dandy’s approach and by 1936 had published ten more cases, and Walker technique was accepted by the surgical community as the favored approach to the pineal region [1].

96

B. A. Muhsen et al.

• In 1929, Max Peet performed the second successful gross total resection of pineal tumor using Dandy’s parieto-occipital transcallosal approach [5, 6]. • Otfrid Foerster, who accomplished the third successful removal of pineal lesion, reporting a technique of occipital craniotomy then puncturing the lateral ventricle to allow decompression and retraction of the occipital lobe from the falx and tentorium [1, 7]. • Van Wagenan introduced right lateral transventricular approach in 1931 [12]. • By the 1960s, the two most common approaches were infratentorial-­supracerebellar routes and the occipital transtentorial or transcallosal approach [8–10].

7.2.1 Supracerebellar-Infratentorial (SCIT) Route1 • It is the most direct pineal surgical route. • It uses an extra-axial plane. • This approach has a special value specifically for the tumors that extend below splenium of corpus callosum into the posterior aspect of third ventricle. • Best indicated for relatively small- to medium-size tumors, those are confined to the midline with rostral/caudal extension in the sagittal plane [26]. • The venous complex is either superior or lateral during the dissection to reach the pineal region. • The use of sitting or modified sitting position will be of great benefit as it will open the corridor during the dissection as the cerebellum will be pulled down by gravity. • It is usually either through midline or paramedian. • The limitations of this approach: –– The very steep tentorium. –– There are difficulties when most of tumor is above tentorium (or vein of Galen) with lateral extension. Surgical Tips • Mayfield head clamp is used. • Sitting or Concorde position with slight head flexion. See Figs.  7.2 and 7.3 (Table 7.1). • Navigation may be applied. • Depending on the case, Frazier burr hole site is prepared as well. • Skin incision in midline 2 cm above inion down to C2. • Retraction with cerebellar retractor to ensure adequate lateral exposure.

 The supracerebellar-infratentorial (SCIT) routes were popularized by Bennett M. Stein in 1971, when he reported six cases of this approach in sitting position under microscope with no perioperative mortality and little morbidity [10]. 1

7  Treatment and Approaches for the Pineal Gland Region

a

97

b

c

Fig. 7.2 (a) Trajectory of the infratentorial-supracerebellar approach. (b) The semisitting position diagram showing upward and forward flexion of the head, keeping two fingerbreadths between the chin and the chest. (c) The burr holes’ site (black circles), craniotomy bone flap in interrupted lines—it’s better not to open down to the foramen magnum and to leave some bone to support the cerebellum. (Cistern magna could be reached to drain CSF with opening of FM) (© illustrated by Meleine Landry Konan, Neurosurgeon, University Felix Houphouet Boigny, Ivory Coast)

a

b

Fig. 7.3  The SCIT approach: (a) the dural opening in v-shaped manner, the upper part of the dura is reflected over the transverse sinus. (b) Microscopic view of the pineal region (T tentorium, VOG vein of Galen, VCI internal cerebral vein, VBR basal vein of Rosenthal, CRBL cerebellum) (© Courtesy of Prof. Vladimír Beneš, Department of Neurosurgery and Neurooncology, First Faculty of Medicine of Charles University, Military University Hospital, Prague, Czech Republic)

98

B. A. Muhsen et al.

Table 7.1  Advantage and disadvantage of supracerebellar infratentorial approach Advantages Extra axial—cisternal pathway Direct route, midline view, and easy orientation

Avoidance of deep veins (dorsal to lesion) Cerebellar retraction by gravity—one spatula sometimes is used above cerebellum only Best indicated for relatively small- to medium-size tumors those are confined to the midline with rostral/caudal extension in the sagittal plane

Disadvantages Not applicable very steep tentorial angle Hard to achieve gross total resection when the lesion extends above (corpus callosum or vein of Galen) + lesion with downward extension in front of cerebellum Hard to reach lesions with extensions above and lateral to tentorial notch (or vein of Galen) Surgeon fatigue with sitting position

Long instruments are needed Risk of air embolism from the sitting position

• Burr holes can be done by one of the following: –– Single burr hole over torcula. –– Two burr holes over the torcula and occipital sinus. –– Four burr holes over torcula, occipital sinus, both transverse sinuses (burr holes before crossing each sinus is possible). • Dura should be freed around the bone edges and in the way of craniotomy with Penfield dissector or Gigli guide. • Craniotomy with careful elevation of bone flap, waxing the bone edges, and meticulous homeostasis should be secured. • Dura should be opened in a U shape and reflected over the transverse sinuses and then start opening over the cerebellar hemispheres and keeping midline at the end; you might need to ligate occipital sinus before you reflect dura and tack up stitch under the tent will give more exposure. • Vermian veins and bridging tentorial veins can be safely scarified, careful dissection of thickened arachnoids around deep circulation veins (venous curtin). Precentral cerebellar vein is sacrificed safely (consider risk of vein of Galen perforation, sometimes confused as precentral cerebellar vein).

7.2.2 P  aramedian Supracerebellar-Infratentorial (SCIT)2 (AKA Lateral SCIT) • Offers safer, faster, and more effective route for pineal region. • This approach may offer advantages over the midline supracerebellar corridor: 2  Gross total resections of 23 lesions were done by Hernesniemi et al. using the paramedian supracerebellar approach [22]. This approach was introduced by Yasargil for the management of aneurysms of  the  superior cerebellar artery [22, 23], Van den Bergh first described this approach for pineal tumors [22, 24].

7  Treatment and Approaches for the Pineal Gland Region

99

Fig. 7.4  The paramedian supracerebellar infratentorial approach (or lateral) utilizes the downward slope of the cerebellum to facilitate exposure (© illustrated by Meleine Landry Konan, Neurosurgeon, University Felix Houphouet Boigny, Ivory Coast)

–– It could be done in sitting position [22] or in lateral position [25]. –– Offer improved visualization and operative angles for resection of the caudal extension of the tumor. –– Less invasive route and minimizing retraction. –– Less need to coagulate vermian or bridging tentorial veins. • This approach may be considered for resection of large pineal region tumors (Fig. 7.4) [25].

7.2.3 Occipital Transtentorial (OTT) Approach3 • This approach is best in lesions with downward extension in front of the cerebellum in the mesencephalic fissure (Fig. 7.5). • Surgeon faces less bridging veins from the occipital lobe to the superior sagittal sinus. • Best for lesions centered at or superior to the tentorial edge (or vein of Galen) or lateral extension beyond the medial borders of the tentorium [26]. • When compared to supracerebellar infratentorial, it allows for wider dissection around tumors or vascular lesions (Tables 7.2 and 7.3) [26, 27]. Surgical Tips • Lateral, three quarter prone (swimmer), sitting or semisitting positions can be used.

3  Occipital transtentorial (OTT) approach was described by Heppner in 1959, popularized by Poppen in  1960 [20] and  then modified by Jamieson in  1971 and  later by Lapras (Capdeville 1974) [21].

100

B. A. Muhsen et al.

Fig. 7.5  The OTT approach: occipital lobe is retracted (© illustrated by Meleine Landry Konan, Neurosurgeon, University Felix Houphouet Boigny, Ivory Coast)

Table 7.2  Advantages and disadvantages of the occipital transtentorial (OTT) approach Advantages Better, wider view above and lateral to tentorial notch lesions Best in lesions with downward extension in front of the cerebellum

Disadvantages Retraction on the occipital lobe—risk of occipital cortical injury Retraction on the corpus callosum—risk of injury

Table 7.3  Comparison between the most commonly utilized approaches SCIT vs. OTT The supracerebellar-infratentorial (SCIT) route Most commonly used Direct approach Sitting or prone position usually Pineal region masses without significant upward (above VOG or tentorium) or downward extension (in front of cerebellum)

Occipital transtentorial (OTT) approach The second popular approach Wider view around lesion Wider venous structure view Lateral position—sitting, semisitting—three quarter prone Preferable if a significant caudal extension in front of cerebellum Preferable if significant extension above tentorium or vein of Galen

7  Treatment and Approaches for the Pineal Gland Region

101

• In lateral or three quarter prone, ipsilateral shoulder down (allow the occipital lobe to fall with gravity) and the head toward the floor. • Lumbar drain may be utilized. • Neuronavigation system may be utilized to locate the venous sinuses. • Midline skin incision from highest parietal point to below inion. • Two burr holes above torcula and on superior sagittal sinus (SSS). • Dura opened and reflected over the SSS. • Tentorium is incised 1 cm lateral to the straight sinus and 2 cm anterior to the transverse sinus. • Care to maintain minimal retraction to avoid occipital lobe injury.

7.2.4 Combined Supra-/Infratentorial Transsinus • Offers supratentorial and infratentorial access • Usually used for very large lesions with extension above and below tentorium especially with solid lesions as meningioma Surgical Tips • Three- or two-pieces craniotomy could be utilized. • This approach includes two dural flaps above and below non-dominant transverse sinus. • Temporary clips could be used, then sharp cut of the non-dominant transverse sinus.

7.2.5 Transcortical Transventricular Approach • • • •

Less commonly used. This approach adds morbidity from cortical incision with limited view. It could be useful with ventricular extension and with dilated ventricles. The cortical incision placed in the posterior part of the superior temporal gyrus or parietal cortex (Fig. 7.6).

7.2.6 I nterhemispheric Parieto-occipital Approach (Transcallosal or Retrocallosal): Introduced by Van Wagenan in 1931 [12] • It is associated with higher rates of mortality and morbidity. • Useful in large pineal region tumors or posterior third ventricular tumors when most of tumor is above the tent or vein of Galen. • Approche modifications were made from the original Dandy approach including retrocallosal approach, falcine, and tentorial incision which made this approach safer and more versatile [26, 28] (Fig. 7.7).

102

B. A. Muhsen et al.

Fig. 7.6  The trajectory of the transcortical transventricular approach

Fig. 7.7  Interhemispheric parieto-occipital transcallosal IHPO approach (dandy approach): demonstration of trajectory of the craniotomy site in sagittal and coronal planes. This approach is very rarely used nowadays

Endoscopic Surgery • Introduced to replace conventional methods of obtaining biopsies of pineal lesions. • It started with transventricular approach, then progressed, and became used in other approaches like supracerebellar infratentorial approach.

7  Treatment and Approaches for the Pineal Gland Region

103

Table 7.4  Comparison of the endoscopic vs. microscopic supracerebellar-infratentorial approach Endoscopic supracerebellar-infratentorial approach Smaller incisions Less approach-related morbidity Shorter surgical time Shorter hospital stay

Microscopic supracerebellar-infratentorial approach Bigger incisions More approach-related morbidity Longer time Longer hospital stay

7.2.7 Endoscopic Transventricular Approach4 • Very useful technique in presence of hydrocephalus as approximately 90% of patients with pineal tumors have hydrocephalus at the time of presentation [13, 14]. • Endoscopy adds the benefit of tissue sampling, increasing the accuracy of biopsy in addition to CSF sampling. • ETV can be done as well to treat hydrocephalus. • Sometimes it is the initial and the only treatment done in such cases. • The possibility of using an assisted endoscopic technique during microsurgical resection of tumors has previously been reported [15–18]. • During the microsurgical procedure, the use of an endoscope will permit the visualization of tumor specimens in the blind operative corners that can be removed either with the help of the endoscope or with the microscope [15]. • The technical limitation of this technique is the presence or absence of hydrocephalus although Yamamoto et  al. reported their experience with a flexible endoscope and Souweidane and Luther reported a series of patients with biopsy without hydrocephalus [15, 16, 19].

7.2.8 Endoscopic Supracerebellar Infratentorial Approach5 • Performed through a small keyhole opening and through the use of high-­ definition fiber-optic technology, reaching the tumor without touching the brain (Table 7.4) [35]. • The advantages of this approach: –– Only a 1.5 -to 2-cm occipital burr hole is needed. –– Shorter surgical time (2 h). –– Shorter hospitalization (48 h) [35]. 4  Fukishima et  al. were the  first who described the  usefulness of  in  the  endoscope for  biopsy in the pineal region [11], and then in 1997 Rohbinson and Cohen who firstly described endoscopic ventriculostomy and  biopsy as  an  alternative to  the  ventriculoperitoneal shunts and  performing a separate biopsy [13]. 5  Purely endoscopic was done first Ruge et al. for fenestration of quadrigeminal region Arachnoid cysts [33, 34] in  1997, then to  resects a  pineal cyst [29, 32] in  2008, then applied to  remove the tumors [30–32].

104

B. A. Muhsen et al.

7.2.9 Endoscopic-Assisted Microsurgical Approach The possibility of using an assisted endoscopic technique during microsurgical resection of tumors has previously been reported [15–18]; during the microsurgical procedure, the use of an endoscope will permit the visualization of tumor specimens in the blind operative corners that can be removed either with the help of the endoscope or with the microscope [15] which will be of value in achieving the gross total resection.

7.3

Pearls in Pineal Region Surgery

–– The following should be considered during preoperative planning for pineal region surgery: Bulk of tumor is above or below tentorium, lateral extent, relation of deep veins with tumor, tentorium steep, solid, or cystic content. –– The precentral cerebellar vein can be divided safely. –– Lesions stuck to the vein of Galen must be left. –– The arachnoid in the pineal region is usually thick, needs careful dissection. And not to be confused from the deep veins. –– Endoscopic surgery can be of great value for this deep-seated region in the brain. –– Management of associated hydrocephalus is with endoscopic third ventriculostomy, permanent shunt, or external ventricular drain (temporary). –– The selection of the surgical approach depends on the lesion location, extension, relation to the Galenic venous complex, tentorial angle, and the surgeon’s experience. In lesions located below the Galenic venous complex, then it would be better approached with infratentorial supracerebellar approach (Fig. 7.8a), others should be approached with other approaches than infratentorial supracerebellar approach due to the very steep tentorial angle (Fig. 7.8b), and some large lesions with both supra- and infratentorial extension may require an occipital transtentorial approach (Fig. 7.8c). –– For summary of pineal region approaches and the major contributor(s) of each approach, see Table 7.5. Questions on Treatment and Approaches for Pineal Region 1. Which of the following is false? A. The two most commonly utilized surgical approaches are SCIT and OTT approaches. B. The SCIT is the most common approach. C. OTT approach is the second most common approach. D. Surgical approaches with endoscopy are evolved and widely used for pineal area. E. The choice of surgical approach must be based on what is the best in surgeon hands beside the patient anatomy.

7  Treatment and Approaches for the Pineal Gland Region

a

105

b

c

Fig. 7.8  Different pineal lesions may require different approaches according to the lesion location, extension, relation to the Galenic venous complex, tentorial angle, and the surgeon experience. (a) Pineal lesion located below the Galenic venous complex. (b) Pineal lesion with both supra and infratentorial extension. (c) Pineal lesion with very steep tentorial angle. (© Courtesy of Prof. Vladimír Beneš, Department of Neurosurgery and Neurooncology, First Faculty of Medicine of Charles University, Military University Hospital, Prague, Czech Republic)

Table 7.5  Summary of pineal region approaches and the major contributor(s) of each approach Approach Infratentorial-supracerebellar midline Supracerebellar-infratentorial paramedian (lateral SCIT) Occipital transtentorial Combined supra/infratentorial transsinus Parieto-occipital transcallosal approach Endoscopic transventricular The endoscopic supracerebellar infratentorial approach

Major contribution Krause, Stein Yasargil, Van den Bergh, Hernesniemi et al. A. Cohen-Gadol Heppner, Poppen, Jamieson, Lapras Sekhar Dandy Fukishima, Rohbinson and Cohen Ruge, Gore PA et al. at Barrow Neurological Institute, Hrayr Shahinian and Yoon Ra

106

B. A. Muhsen et al.

2. Which of the following is true? A. During the SCIT, the veins are inferior during the dissection to reach the pineal region. B. SCIT has a value for tumors extending into the posterior aspect of third ventricle. C. During SCIT, concord position is of great benefit as it will open the corridor during the dissection, and it is the usual position. D. SCIT best indicated for relatively large size tumors. E. In SCIT one of the limitations is the caudal/rostral extension of the mass. 3. During SCIT which of the following is false? A. The skin incision is applied in the midline 2 cm above inion down to above foramen magnum. B. Surgeon can use single, two, or even four burr holes to do craniotomy. C. When the dura is opened, start opening over the cerebellar hemispheres and keep midline at the end. D. Vermian and paramedian cerebellar veins can be sacrificed safely. E. Tack up stitch under the tent will give more exposure. 4. Which of the following is true? A. Midline SCIT offers more advantages over paramedian. B. Paramedian SCIT needs to coagulate bridging veins more than midline SCIT. C. Paramedian SCIT can be used for large tumors. D. Paramedian SCIT has a high rate for injury of torcula. E. All of the above. 5. Regarding OTT which of the following is false? A. OTT is best for lesions that extend in front of the cerebellum. B. OTT is best for lesions that extend in the mesencephalic fissure. C. OTT best for lesions centered at or superior to the tentorial edge. D. When compared to OTT, SCIT allows for wider dissection around tumors or vascular lesions. E. During OTT, there are fewer bridging veins to deal with. 6. Regarding OTT, which of the following is true? A. In three-quarter position, the contralateral shoulder is down. B. Tumor debulking usually occurs between the ipsilateral internal cerebral vein and the basal vein of Rosenthal. C. Tentorium is incised 2 mm from the straight sinus. D. OTT offer less retraction on the corpus callosum. E. Compared to OTT, SCIT gives a wider venous structure view. 7. Which of the following is false? A. Combined supra-infratentorial approach is preferred for pineal meningioma. B. Combined supra-infratentorial approach includes two dural flaps above and below non-dominant transverse sinus. C. In transcortical transventricular approach, the cortical incision in the posterior part of the superior temporal gyrus. D. Interhemispheric parieto-occipital approach is useful in large pineal region tumors when most of the tumor is above the vein of Galen.

7  Treatment and Approaches for the Pineal Gland Region

107

E. Transcortical transventricular approach is a commonly used approach for pineal area. 8 . Which of the following is false? A. As 90% of pineal tumor present with hydrocephalus, endoscopic transventricular approach can be used safely. B. Endoscopic approach cannot be used in absence of hydrocephalus. C. The endoscopy adds the values of tissue sampling with increased the accuracy of biopsy. D. Endoscopic SCIT approach can reach the tumor without touching the brain. E. Endoscopic SCIT approach has a shorter surgical time. Answers 1. D. 2. B. 3. A. 4. C. 5. D. 6. D. 7. E. 8. B.

References 1. Choudhry O, Gupta G, Prestigiacomo CJ. On the surgery of the seat of the soul: the pineal gland and the history of its surgical approaches. Neurosurg Clin. 2011;22(3):321–33. 2. Oppenheim H, Krause F.  Operative ErfolgebeiGeschwiilsten der Schhugel—und Vierhugelgegend. Bed Klin Wschr. 1913;50:2316–22. 3. Dandy WE.  An operation for the removal of pineal tumors. Surg Gynecol Obstet. 1921;33:113–9. 4. Pendl G.  The surgery of pineal lesions—historical perspective. Diagnosis and treatment of pineal region tumors. Baltimore: Williams & Wilkins; 1984. p. 139–54. 5. Camins MB, Schlesinger EB. Treatment of tumors of the posterior part of the third ventricle and the pineal region: a long term follow-up. Acta Neurochir. 1978;40(1–2):131–43. 6. Horrax G. Extirpation of a huge pinealoma from a patient with pubertas praecox: a new operative approach. Arch Neurol Psychiatr. 1937;37(2):385–97. 7. Foerster O.  Ein fall von vierhfigeltumordurch operation entfernt. Nervenkr Arch Psychiat. 1928;84:515–6. 8. Isamat F.  Tumors of the posterior part of the third ventricle: neurosurgical criteria, vol. 6. New York: Springer; 1979. 9. Rozario R, Adelman L, Prager RJ, Stein BM.  Meningiomas of the pineal region and third ventricle. Neurosurgery. 1979;5(4):489–95. 10. Stein BM.  The supracerebellar infratentorial approach to pineal lesions. J Neurosurg. 1971;35(2):197–202. 11. Fukushima T, Ishijima B, Hirakawa K, Nakamura N, Sano K.  Ventriculofiberscope: a new technique for endoscopic diagnosis and operation. J Neurosurg. 1973;38(2):251–6. 12. Van Wagenen WP. A surgical approach for the removal of certain pineal tumors. Report of a case. Surg Gynecol Obstet. 1931;53:216–20.

108

B. A. Muhsen et al.

13. Robinson S, Cohen AR. The role of neuroendoscopy in the treatment of pineal region tumors. Surg Neurol. 1997;48(4):360–7. 14. Regis J, Bouillot P, Rouby-Volot F, Figarella-Branger D, Dufour H, Peragut JC. Pineal region tumors and the role of stereotactic biopsy: review of the mortality, morbidity, and diagnostic rates in 370 cases. Neurosurgery. 1996;39(5):907–14. 15. Mottolese C, Szathamari A, Beuriat PA, Grassiot B, Simon E.  Neuroendoscopy and pineal tumors: a review of the literature and our considerations regarding its utility. Neurochirurgie. 2015;61(2–3):155–9. 16. Soweidane M, Luther N. Endoscopic resection of solid intraventricular tumors. J Neurosurg. 2006;105:271–8. 17. Chibbaro S, Di Rocco F, Makiese O, Reiss A, Poczos P, Mirone G, Servadei F, George B, Crafa P, Polivka M, Romano A. Neuroendoscopic management of posterior third ventricle and pineal region tumors: technique, limitation, and possible complication avoidance. Neurosurg Rev. 2012;35(3):331–40. 18. Shirane R, Shamoto H, Umezawa K, Su CC, Kumabe T, Jokura H, Yoshimoto T.  Surgical treatment of pineal region tumors through the occipital transtentorial approach: evaluation of the effectiveness of intra-operative micro-endoscopy combined with neuronavigation. Acta Neurochir. 1999;141(8):801–8. 19. Yamamoto M, Oka K, Takasugi S, Hachisuka S, Miyake E, Tomonaga M. Flexible neuroendoscopy for percutaneous treatment of intraventricular lesions in the absence of hydrocephalus. Minim Invasive Neurosurg. 1997;40(04):139–43. 20. Poppen JL. The right occipital approach to a pinealoma. J Neurosurg. 1966;25(6):706–10. 21. Moreau JJ, Ravon R, Caix M, Salamon G, Brassier G, Velut S. Anatomical basis of the microsurgical approach to the pineal gland. Anat Clin. 1985;7(1):3–13. 22. Choque-Velasquez J, Colasanti R, Resendiz-Nieves JC, Jahromi BR, Kozyrev DA, Thiarawat P, Hernesniemi J.  Supracerebellar infratentorial paramedian approach in Helsinki neurosurgery: cornerstones of a safe and effective route to the pineal region. World Neurosurg. 2017;105:534–42. 23. Yasargil MG. Paramediansupracerebellar approach. In: Microneurosurgery, vol. I. New York: Georg Thieme Verlag; 1984. p. 242. 24. Van den Bergh R. Lateral-paramedian infratentorial approach in lateral decubitus for pineal tumors. Clin Neurol Neurosurg. 1990;92(4):311–6. 25. Kulwin CG, Matsushima K, Malekpour M, Cohen-Gadol AA. Lateral supracerebellar infratentorial approach for microsurgical resection of large midline pineal region tumors: techniques to expand the operative corridor. J Neurosurg. 2016;214(1):269–76. 26. Little KM, Friedman AH, Fukushima T. Surgical approaches to pineal region tumors. J Neuro-­ Oncol. 2001;54(3):287–99. 27. Clark WK, Batjer HH. The occipital transtentorial approach. In: Apuzzo MLJ, editor. Surgery of the third ventricle. Baltimore, MD: Williams and Wilkins; 1998. p. 721–42. 28. McComb JG, Levy ML, Apuzzo ML. The posterior intrahemispheric retrocallosal and transcallosal approaches to the third ventricle region. In: Apuzzo MLJ, editor. Surgery of the third ventricle. Baltimore, MD: Williams & Wilkins; 1998. p. 743. 29. Gore PA, Gonzalez LF, Rekate HL, Nakaji P.  Endoscopic supracerebellar infratento rial approach for pineal cyst resection: technical case report. Operative Neurosurg. 2008;62(suppl_1):ONSE108–9. 30. Sood S, Hoeprich M, Ham SD. Pure endoscopic removal of pineal region tumors. Childs Nerv Syst. 2011;27(9):1489–92. 31. Zanini MA, Rondinelli G, Fernandes AY. Endoscopic supracerebellar infratentorial parapineal approach for third ventricular colloid cyst in a patient with quadrigeminal cistern arachnoid cyst: case report. Clin Neurol Neurosurg. 2013;115(6):751–5. 32. Chaussemy D, Cebulla H, Coca A, Chibarro S, Proust F, Kehrli P. Interest and limits of endoscopic approaches for pineal region tumors. Neurochirurgie. 2015;61(2–3):160–3.

7  Treatment and Approaches for the Pineal Gland Region

109

33. Ruge JR, Johnson RF, Bauer J. Burr hole neuroendoscopic fenestration of quadrigeminal cistern arachnoid cyst: technical case report. Neurosurgery. 1996;38(4):830–7. 34. Zaidi HA, Elhadi AM, Lei T, Preul MC, Little AS, Nakaji P. Minimally invasive endoscopic supracerebellar-infratentorial surgery of the pineal region: anatomical comparison of four variant approaches. World Neurosurg. 2015;84(2):257–66. 35. Shahinian H, Ra Y. Fully endoscopic resection of pineal region tumors. J Neurolog Surg Part B. 2013;74(03):114–7.

8

Interesting Cases of Pineal Gland Diseases and Surgery Gobran Taha Al-Fotih and Samer S. Hoz

The diversity of pineal gland lesions implies frequent emergence of relatively unexpected presentations, pathologies, complications, or even recurrences. In this chapter, we are highlighting 10 of the most unique reported cases related to the pineal gland out of 200 reports which we explored in literature, aiming to enrich the neurosurgeon’s orientation while managing pineal pathologies.

8.1

 arkinsonism as a Manifestation of Pineal P Region Pathology

Parkinsonian-like syndromes can be a rare manifestation of brain tumors. There are several reports regarding meningiomas, posterior fossa cysts or tumors, and chronic subdural hematomas associated with Parkinsonism [1–4]. Two interesting cases of pineal region tumor causing Parkinsonism are reported below.

8.1.1 Case A Scenario A female in her late 50s presented with headache and double vision of few months duration. CT scans showed a hyper-dense, partially enhancing pineal mass, with hydrocephalus. A ventriculoperitoneal shunt surgery was performed, and then a biopsy was obtained which suggested an old hematoma. The patient was doing well for 1 year, and then she develops resting tremor, gate difficulties, and bradykinesia. She was treated for Parkinsonism for few months, but the symptoms gradually G. T. Al-Fotih (*) Department of Neurosurgery, Al-Thawra Modern General Hospital, Sana’a, Yemen S. S. Hoz Neurosurgery Teaching Hospital, Baghdad, Iraq e-mail: [email protected] © Springer Nature Switzerland AG 2020 S. S. Hoz et al. (eds.), Pineal Neurosurgery, https://doi.org/10.1007/978-3-030-53191-1_8

111

112

G. T. Al-Fotih and S. S. Hoz

increased in severity. A new CT scan showed images similar to the first one. She underwent surgery with total removal of the tumor, and the histopathology revealed a cavernoma [5].

8.1.2 Case B Scenario A 14-year-old boy presented with headache of 1  month duration, associated with poor writing and poor school performance. The examination showed a mask face appearance, bradykinesia, ataxic gait, dysdiadochokinesia, and the triad of Parinaud’s syndrome. Serum AFP was elevated to 70 μg/L. Brain MRI revealed a pineal region tumor extending to the thalamus with acute hydrocephalus (which was urgently shunted). Stereotactic biopsy showed immature pineal teratoma, which was treated with resection and chemotherapy. The AFP was normalized, and the patient got better. After 3 months, he developed tremor, rigidity, urine incontinence, dysphagia, and dysarthria. He was treated with Parkinson medications, with consequent mild improvement. The follow-up MRI showed recurrence of the tumor, which was treated via stereotactic radiosurgery. He died later due to systemic illness [6].

8.1.3 Learning Points Parkinsonism can be attributed to a tumor’s infiltration of the nigro-striate-­ pallidal system.

8.2

 eversible Pure Word Deafness due to Inferior Colliculi R Compression by a Pineal Germinoma in a Young Adult

Pure word deafness is a rare subtype of central deafness, characterized by the impairment of spoken language comprehension and repetition, whereas identification of nonverbal sounds as well as reading and writing are unaffected (Fig. 8.1) [7].

8.2.1 Case Scenario A young male presented with headache and triad of Parinaud’s syndrome. Serum AFP and B-HCG were normal, and MRI showed a pineal tumor with hydrocephalus. Endoscopic biopsy revealed germinoma. The symptoms were relieved after a third ventriculostomy procedure. Then after 2  weeks, he developed tinnitus and hearing impairment, and pure tone audiometry revealed slight hearing loss with 45 dB in right ear and 30 dB in left ear. Speech discrimination was significantly impaired with 70% and 50% for right and left ears, respectively, at 70 dB SPL. A significant compression of the inferior colliculi by the tumor was seen in the new CT. The patient was treated with radiotherapy; the symptoms resolved completely, and MRI showed tumor size reduction [8].

8  Interesting Cases of Pineal Gland Diseases and Surgery Fig. 8.1  Tumors in pineal gland can compress the inferior colliculi. (a) The pineal gland, (b) the inferior colliculus (© Courtesy of Luis R. Moscote-Salazar, Department of Neurosurgery, University of Cartagena, Colombia)

113

A B

8.2.2 Learning Points Pure word deafness is commonly seen in temporal region lesions and may be seen in inferior colliculi lesions too. Pineal tumors may impair the thalamocortical auditory pathways via compression of the medial geniculate bodies and the internal capsule.

8.3

 pontaneous Regression of Pineal Lesions: Ghost S Tumor vs. Pineal Apoplexy

Treatment protocols of pineal region tumors including radical surgery, chemotherapy, and radiotherapy largely depend on the biochemical and histological diagnoses. Spontaneous tumor regression before applying any of the abovementioned protocols, although rare, is known to occur in patients with testicular seminomas. There are also examples of occasional spontaneous regression of a pineal germinoma [9]. Below are three case scenarios of spontaneous regression of pineal region tumors, either after minor manipulation of the tumor to obtain a biopsy or without any intervention.

8.3.1 Case A Scenario A 15-year-old female presented with photophobia and diplopia of 3 months, followed by signs of raised ICP.  Imaging studies showed a pineal tumor associated

114

G. T. Al-Fotih and S. S. Hoz

with hydrocephalus. No blood or CSF markers for germinal tumors were detected. However, lymphoid elements were detected. The signs and symptoms disappeared before starting the treatment, and an MRI performed 1 month later revealed tumor size reduction and no hydrocephalus. In the next follow-up, the patient was clinically stable, and there was no tumor recurrence [10].

8.3.2 Case B Scenario A 12-year-old female had a presentation of headache associated with nausea and vomiting; brain MRI showed a cystic pineal mass with ring enhancement and hydrocephalus. She was treated with third ventriculostomy without biopsy. The hydrocephalus was resolved in the postoperative CT scan, and the mass was the same size. However, the mass disappeared in the next MRI which was done 3 months later. No complications were detected in the next 5 years [10].

8.3.3 Case C Scenario An infant baby was admitted due to enlarged head circumference, with no other neurological findings. The brain MRI showed a homogeneous solid mass in the pineal region with hydrocephalus. The baby was treated with ventriculostomy and tumor biopsy, which revealed a low-grade neuroglial tumor. No further treatment was administered until the follow-up MRI, which showed a complete tumor disappearance; no recurrence was detected for the next 10 years [10].

8.3.4 Learning Points Spontaneous tumor regression may be due to apoplexy of the pineal gland. Other mechanisms, however, should be considered and investigated. Wait-and-see policy can be considered in some cases.

8.4

Pineal Region Schwannoma

Schwannomas are benign tumors of Schwann cell origin and are the most common tumors of peripheral nerves and common posterior fossa. Schwannoma of the trochlear nerve can occur in any location. We found less than 35 cases of trochlear nerve schwannoma in the literature, but none had reported IV nerve schwannoma in the pineal region.

8.4.1 Case Scenario A young lady presented with headache with no other symptoms, and no abnormalities in the neurological examination. Brain CT and MR imaging showed

8  Interesting Cases of Pineal Gland Diseases and Surgery

115

hydrocephalus due to a pineal mass. Serum B-HCG and AFP were normal. She underwent surgery for ventriculostomy and tumor resection. Histopathology revealed a trochlear nerve schwannoma [11].

8.4.2 Learning Points Schwannoma of the pineal region is very rare but can still occur, and should be considered when a pineal mass shows an atypical presentation or imaging.

8.5

Pineal Region Craniopharyngioma

Craniopharyngiomas are the most common intracranial pediatric tumors of nonglial origin; they constitute 1.2–4% of all brain tumors and 6–9% of all pediatric brain tumors [11]. These tumors generally can be found in the suprasellar region or in both the suprasellar and the intrasellar regions and in the third ventricle. But the development of craniopharyngioma in the pineal region is unusual [11].

8.5.1 Case Scenario An 8-year-old child was admitted due to occipital headache with vomiting and diplopia; on examination he showed left trochlear and oculomotor nerve palsy and a positive Romberg’s sign. Brain MRI showed large pineal mass associated with hydrocephalus. Ventriculostomy was done, followed by resection of the tumor on the next day. During surgery, the tumor was yellowish in color and firm in consistency, with a cartilage-like structure containing a little yellowish green fluid, and it was totally removed. The histopathology confirmed adamantinomatous craniopharyngioma [12].

8.5.2 Learning Points Craniopharyngioma may extend from third ventricle to pineal region.

8.6

 ineal Diffuse Large B-Cell Lymphoma Concomitant P with Pituitary Prolactinoma

Lymphoma may involve the central nervous system (CNS) as an isolated brain, ocular, or leptomeningeal condition (primary CNS lymphoma) or as a neurological complication of systemic lymphoma (secondary CNS lymphoma). Congenital or acquired immunodeficiency is the only established risk factor for primary CNS lymphoma (PCNSL). Primary CNS lymphoma appears in approximately 1–2% of patients with non-Hodgkin lymphoma [11]. Systemic lymphoma spreads to the CNS in 5.5–9.4% of cases and is associated with a poor prognosis [13].

116

G. T. Al-Fotih and S. S. Hoz

Neuroendocrine and immune responses can affect each other via various interactions between the hormones and respective receptors and the immune system. Studies showed elevated prolactin levels are associated with the progression of hematologic diseases including multiple myeloma, acute myeloid leukemia, and non-Hodgkin lymphoma [14]. Below is a case of pineal lymphoma concomitant with pituitary prolactinoma by YJ Kim et al.

8.6.1 Case Scenario A 51-years-old age male presented with severe headache, nausea, vomiting, memory loss, and Parinaud’s syndrome on examination. MRI showed hydrocephalus, with a heterogeneous enhancing pineal mass extending to hypothalamus and midbrain; a sellar lesion that enlarged the sella was also seen. Blood investigations including pineal tumor markers were normal, apart from hyperprolactinemia. The pineal mass was totally removed after frozen section suggested a pineoblastoma. Two weeks postoperatively, the patient developed gastric symptoms with vomiting, and abdominal CT imaging showed gastric wall thickening. A gastric biopsy was taken, revealing a diffuse large B-cell lymphoma. The prolactin level dropped within 3 months after brain surgery. The brain tumor biopsy confirmed diffuse large B-cell lymphoma. The patient died after 6 months [15].

8.6.2 Learning Points Metastasis to the pineal region is rare and is potentially attributed to a lacking blood–brain barrier. Lymphoma’s development may be stimulated by micro-­ environmental alterations or hormones produced by the pituitary adenoma. The exact mechanism is not well understood. The presence of elevated serum PRL levels in the context of hematological malignancy is still controversial.

8.7

 ecurrent Intracranial Germinoma Along R the Endoscopic Ventriculostomy Tract

Germinoma may metastasize via CSF to other locations, but metastasis thorough endoscopic tract is rare. Below is a case report of a recurrent intracranial germinoma along the site of an endoscopic third ventriculostomy (ETV) after complete local tumor control using radiation therapy.

8.7.1 Case Scenario A 13-year-old female presented with signs of raised ICP and Parinaud’s syndrome. Brain imaging showed hydrocephalus with enhancing pineal mass.

8  Interesting Cases of Pineal Gland Diseases and Surgery

117

Serum B-HCG and AFP were elevated. The girl was treated with ventriculostomy and biopsy which revealed a germinoma, followed by chemotherapy and radiotherapy. Ten months after surgery, there was tumor size reduction in MRI and a normalization of B-HCG.  In the MRI that performed after 1  year, the tumor disappeared, but there was an extra axial mass at the site of the ETV burr hole. The mass was resected and the biopsy confirmed germinoma as the primary pineal lesion [16].

8.7.2 Learning Points Germinoma can metastasize via CSF or implantation procedures. Implantation metastasis has been reported in other tumors such as malignant glioma, lymphoma, craniopharyngioma, pineoblastoma, malignant rhabdoid tumor, and cavernous hemangioma. Follow-up imaging is recommended in these types of tumors.

8.8

I ntracranial Germinoma in the Pineal Region Arising After Subtotal Resection of Epidermoid Cyst

Epidermoid cysts or tumors are benign congenital lesions that may arise in the spine or intracranially. Intracranial epidermoid cysts account for 0.2–1.8% of all intracranial tumors [17]. They generally occur in the cerebellopontine angle or in the parasellar cisterns. Epidermoid cysts of the pineal region are rare and comprise only 1.6% of pineal region masses in pediatric patients [17]. Epidermoid cysts may go into malignant degeneration into squamous cell carcinoma. Twenty cases of leptomeningeal dissemination of squamous cell carcinoma arising in an epidermoid cyst have been reported [18]. Below is a rare case report of germinoma arising adjacent to an epidermoid cyst in the pineal region.

8.8.1 Case Scenario A 16-year-old boy presented with headache; brain MRI revealed a pineal mass which was non-enhancing with restricted diffusion. The mass was resected with small calcified anterior and superior parts left residuals. The histopathology confirmed an epidermoid cyst. After 14  months the patient redeveloped headache, with recurrence of the cyst in MRI. The mass was resected, and the biopsy showed epidermoid cyst as well. Three months later, the patient developed severe headache with blurred vision and fever; MRI showed an enhancing pineal mass, and tumor resection was achieved stereotactically; the mass had an epidermoid appearance, but the enhancing part was sent as an isolated specimen for histopathology, and the biopsy result was germinoma mixed with epidermoid cyst [19].

118

G. T. Al-Fotih and S. S. Hoz

8.8.2 Learning Points Epidermoids are most commonly found in the cerebellopontine angle and are the third most common tumor in that location after vestibular schwannomas and meningiomas. Diffusion-weighted imaging sequences can easily distinguish epidermoid from other pathologies. Malignant transformation of epidermoid cyst is rare. Gross total resection of epidermoid cyst is often difficult.

8.9

Spinal Metastasis of Pineal Glioblastoma Multiforme

Arising from the surrounding glial stroma, glioblastoma is very rare in the pineal region, and metastasis to the spinal region is even rarer. Here, Birbilis TA et  al. reported a case of pineal gland GBM with drop-like metastasis to the spine.

8.9.1 Case Scenario A 57-year-old age lady is presented with low back pain, gait difficulty, and urine incontinence of 3 months. Three years prior to that, she had developed pineal GBM which was treated with biopsy, chemotherapy, radiotherapy, and a VP shunt. There was no tumor growth in the follow-up MRI. The examination revealed spasticity of the lower limbs, a sensory deficit below C8 level, and positive Babinski sign bilaterally. Spinal MRI showed enhancing intramedullary lesion extending from C7 to T3 levels. A biopsy taken from the lesion confirmed a GBM diagnosis (WHO grade IV). Patient died after few weeks due to rapid deterioration [20].

8.9.2 Learning Points Malignant glioblastomas multiformes of the pineal region are rare. Primary GBM of the central nervous system has a generally poor prognosis, with median survival after diagnosis of 10–12 months [21]. Close examination of MRI studies of patients with pineal region masses is very important, and evidence of leptomeningeal or ventricular dissemination should increase the suspicion for GBM metastasis.

8.10 L  ate Recurrence 21 Years After Total Removal of Immature Teratoma Immature teratoma contains incompletely differentiated components resembling fetal tissues and has a much higher recurrence rate than mature teratoma. Because

8  Interesting Cases of Pineal Gland Diseases and Surgery

119

immature teratoma has a high recurrence rate, combined radio-/chemotherapy is recommended post operation. Late recurrence of immature teratoma is not common, in contrast to germinoma, which may recur more than 20 years after initial treatment [22]. Below is a case report about immature teratoma which recurred 21 years later after complete resection.

8.10.1 Case Scenario A male baby was admitted due to signs of raised ICP and Parinaud’s syndrome; brain imaging showed hydrocephalus and a heterogeneous enhancing pineal mass; serum and CSF B-HCG and AFP were normal. The tumor was resected, and a biopsy confirmed a mature teratoma. There was no recurrence in the follow-up MRI for 21 years, then he developed severe headache. The MRI showed a homogeneous enhancing pineal mass. MRS was obtained and suggested a tumor with high lipid peak. Serum markers were normal but the CSF cytology showed atypical cells that contain granular chromatin and irregular nucleoli in large nuclei. A recurrence was suspected, so the first biopsy was reexamined revealing an immature teratoma (rather than mature) with CSF dissemination. A diagnosis of germinoma was suggested, and the patient was sent for chemotherapy and radiotherapy; in the follow­up MRI, the tumor completely disappeared [22, 23].

8.10.2 Learning Points Gross total resection is decisive for successful treatment of immature teratoma. Adjuvant chemotherapy and radiotherapy are generally recommended even after total resection of immature teratoma due to the high recurrence rate. Mature teratoma is considered curable with total resection only, but meticulous histological examination is essential to accurately characterize mature teratomas. Immature teratoma may recur as germinoma.

8.11 Summary Studying the spectrum of pineal diseases and their management necessitates knowledge of reported cases which are rare, whether in terms of having unusual presentation, pathologies, or disease course, as this might ultimately lead to improved patient survival and overall outcome. Acknowledgment  Professor Marcos Tatagiba (Germany) and Professor FangCheng Li (China) for their support and valuable advices during the writing of this chapter.

120

G. T. Al-Fotih and S. S. Hoz

References 1. Kondo T. Brain tumor and parkinsonism. Nihon rinsho. Japan J Clin Med. 1997;55(1):118–22. 2. Wakai S, Nakamura K, Niizaki K, Nagai M, Nishizawa T, Yokoyama S, Katayama S.  Meningioma of the anterior third ventricle presenting with parkinsonism. Surg Neurol. 1984;21(1):88–92. 3. de Vera Reyes JA. Parkinsonian-like syndrome caused by posterior fossa tumor: case report. J Neurosurg. 1970;33(5):599–601. 4. Syndyk R, Khan I. Parkinsonism due to subdural hematoma. J Neurosurg. 1993;58:298–9. 5. Vhora S, Kobayashi S, Okudera H. Pineal cavernous angioma presenting with parkinsonism. J Clin Neurosci. 2001;8(3):263–6. 6. Dolendo MC, Lin TP, Tat OH, Chong QT, Timothy LK. Parkinsonism as an unusual presenting symptom of pineal gland teratoma. Pediatr Neurol. 2003;28(4):310–2. 7. Shivashankar N, Shashikala HR, Nagaraja D, Jayakumar PN, Ratnavalli E. Pure word deafness in two patients with subcortical lesions. Clin Neurol Neurosurg. 2001;103(4):201–5. 8. Joswig H, Schönenberger U, Brügge D, Richter H, Surbeck W. Reversible pure word deafness due to inferior colliculi compression by a pineal germinoma in a young adult. Clin Neurol Neurosurg. 2015;139:62–5. 9. Ide M, Jimbo M, Yamamoto M, Hagiwara S, Aiba M, Kubo O.  Spontaneous regression of primary intracranial germinoma: a case report. Cancer. 1997;79(3):558–63. 10. Mattogno PP, Frassanito P, Massimi L, Tamburrini G, Novello M, Lauriola L, Caldarelli M.  Spontaneous regression of pineal lesions: ghost tumor or pineal apoplexy? World Neurosurg. 2016;88:64–9. 11. Chaudhry NS, Ahmad FU, Morcos JJ. Pineal region schwannoma arising from the trochlear nerve. J Clin Neurosci. 2016;32:159–61. 12. Usanov EI, Hatomkin DM, Nikulina TA, Gorban NA. Craniopharyngioma of the pineal region. Childs Nerv Syst. 1999;15(1):4–7. 13. Loeffler JS, Ervin TJ, Mauch P, Skarin A, Weinstein HJ, Canellos G, Cassady JR.  Primary lymphomas of the central nervous system: patterns of failure and factors that influence survival. J Clin Oncol. 1985;3(4):490–4. 14. Hollender A, Kvaloy S, Lote K, Nome O, Holte H. Prognostic factors in 140 adult patients with non-Hodgkin’s lymphoma with systemic central nervous system (CNS) involvement. A single Centre analysis. Eur J Cancer. 2000;36(14):1762–8. 15. Gadó K, Pállinger E, Kovács P, Takács E, Szilvási I, Tóth BE, Nagy G, Domján G, Falus A.  Prolactin influences proliferation and apoptosis of a human IgE secreting myeloma cell line, U266. Immunol Lett. 2002;82(3):191–6. 16. Kim YJ, Kim HK, Yang DH, Jung S, Noh MG, Lee JH, Lee KH, Moon KS. Pineal diffuse large B-Cell lymphoma concomitant with pituitary prolactinoma: possible correlation between 2 distinguished pathologies: a case report. Medicine. 2016;95(8):e2923. 17. Choi BK, Cha SH, Song GS, Choi CH, Lee SW, Lim YT, Kim WT.  Recurrent intracranial germinoma along the endoscopic ventriculostomy tract: case report. J Neurosurg Pediatr. 2007;107(1):62–5. 18. MacKay CI, Baeesa SS, Ventureyra EC. Epidermoid cysts of the pineal region. Childs Nerv Syst. 1999;15(4):170–8. 19. Pagni F, Brenna A, Leone BE, Vergani F, Isimbaldi G. Malignant epidermoid cyst of the pineal region with lumbar metastasis. Neuropathology. 2007;27(6):566–9. 20. Walker AJ, Huynh-Le MP, Nauen D, Malayeri AA, Jallo G, Terezakis SA. Intracranial germinoma in the pineal region arising after subtotal resection of epidermoid cyst: case report. Childs Nerv Syst. 2014;30(5):963–6.

8  Interesting Cases of Pineal Gland Diseases and Surgery

121

21. Birbilis TA, Matis GK, Eleftheriadis SG, Theodoropoulou EN, Sivridis E. Spinal metastasis of glioblastoma multiforme: an uncommon Lacroix M, Abi-said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, Hess K. a multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg. 2001;95(2):190–8. 22. Kamoshima Y, Sawamura Y, Ikeda J, Shirato H, Aoyama H. Late recurrence and salvage therapy of CNS germinomas. J Neuro-Oncol. 2008;90(2):205. 23. Mano Y, Kanamori M, Kumabe T, Saito R, Watanabe M, Sonoda Y, Tominaga T. Extremely late recurrence 21 years after total removal of immature teratoma: a case report and literature review. Neurol Med Chir (Tokyo). 2017;57(1):51–6.

9

Animal Based Surgical Training in Pineal Approaches Samer S. Hoz, Rami Darwazeh, Mohammed Sabah Abdulqader, Osama Majeed Alaawadi, Gulshan Talat Muhammed, Awfa Aktham Abdullateef, Aysar Khudhair Jassam, Alyaa Khadim Abdulreda, and Hayder Ali Al-Saadi 9.1

Introduction

Residents may take years to master the required surgical skills to operate with sufficient patient safety, and this renders laboratory-based training models fundamental for optimized surgical training ahead of a self-reliant clinical career. Ideally, a novice trainee would begin training with nonbiological material, and after gaining sufficient dexterity, the trainee will be able to practice on biological materials followed by high-fidelity models prior to actual surgery. Unfortunately, the effectiveness of each model has, to our knowledge, only been judged subjectively, and we argue that objective quantification methods might be necessary to accelerate the acquisition of competence. Like any surgical specialty, neurosurgery requires the development of dexterity and skills for basic up to difficult techniques and procedures. In delicate organs such as the central nervous system, the neurosurgeon’s individual skills play a crucial role in preventing complications and determining patient outcome. Today, there is a multitude of training models and highly sophisticated simulation devices dedicated for improving surgical skills. The implementation of modern

S. S. Hoz (*) Neurosurgery Teaching Hospital, Baghdad, Iraq e-mail: [email protected] R. Darwazeh Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China M. S. Abdulqader · O. M. Alaawadi · G. T. Muhammed · A. A. Abdullateef · A. K. Jassam A. K. Abdulreda · H. A. Al-Saadi Department of Neurosurgery, Neurosurgery Teaching Hospital, Baghdad, Iraq e-mail: [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected] © Springer Nature Switzerland AG 2020 S. S. Hoz et al. (eds.), Pineal Neurosurgery, https://doi.org/10.1007/978-3-030-53191-1_9

123

124

S. S. Hoz et al.

state-of-the-art devices has been found to positively impact the resident’s learning process, but the associated high cost of acquiring and maintaining such modalities renders this approach of limited applicability for most surgical departments [1]. Despite its unquestioned general value in surgical training, the use of human cadaver training models is also subject to significant challenges like the limited availability and the sophisticated techniques used for their preservation, along with considerable associated expenses. The use of fresh animal cadavers offers a lower-cost alternative. Several nonliving animal models have been developed to help residents gain experience with microneurosurgical procedures, especially in the region of the posterior fossa. However, none of these has explicitly included the pineal region as an essential anatomical landmark for identification, dissection, and application of real-­ life surgical scenarios [2–5]. From a clinical point of view, microneurosurgical approaches to the pineal gland region are particularly challenging. Due to the variety of approaches and the low volume of cases encountered during residency, it is naturally challenging for residents to obtain sufficient experience with lesions of the pineal region, leading to difficulties in anatomical orientation and in conducting the proper surgical steps. As far as animal models are considered, there are striking similarities between human and sheep with regard to the pineal region and its related venous complex. This is why several studies were designed to exploit these similarities, including pinealectomy trials on living sheep to study the functions of the pineal gland. In sheep, the pineal gland is hidden at the bottom of the cerebral transverse fissure in a medial position. As with humans, the gland is located inferior to the vein of Galen, superior to the quadrigeminal plate of the midbrain, anterior to the rostral colliculi, and within the arachnoid. One significant anatomical difference is related to the tentorium; in sheep, the tentorium runs parallel to the neck, unlike its more perpendicular relationship in humans. Owing to this relationship, the midbrain in this model can be approached anteriorly to the tentorium without necessarily having to open the latter, unlike with humans [6–12]. In the recent years, some scholars have adopted effective training models based on nonliving sheep. The fresh sheep head serves as a simulation model that can be used in a neurosurgery skill laboratory, for training residents on the basic steps of common microneurosurgical approaches to pineal region pathologies [13–16]. Both supracerebellar infratentorial and occipital transtentorial approaches are included in the training program as they are considered the standard access trajectories to the pineal region. The midline supracerebellar infratentorial approach was first described by Horsley and Krause and was refined by Stein in 1971 [17]. For many neurosurgeons, it is considered the “working horse” for lesions of the pineal region, but it cannot be used if the angle of the tentorium is too steep (best assessed on MRI). Depending on the surgeon’s preference, it may be conducted in the concord or in the sitting position, with the latter being associated with a higher risk of air embolism. Compared to the supracerebellar infratentorial approach and depending on the individual patient anatomy, the occipital transtentorial approach offers an even wider view of the pineal region. It is recommended for lesions centered at or

9  Animal Based Surgical Training in Pineal Approaches

125

superior to the tentorial edge, located above the vein of Galen, or for cystic lesions with superior extension. Its drawbacks include the risk of injury to the occipital visual cortex and the splenium of the corpus callosum [18–22].

9.2

The Sheep Head Model

In most countries, the material for the model is obtained from a local butcher and consists of a fresh sheep cranium. The sheep head is kept in a refrigerator at 4 °C for 6 h after the specimen has been obtained. Before the microneurosurgical procedure, all muscles overlying the suboccipital region are manually removed. The head is firmly fixed into a Mayfield head clamp that is withdrawn from use in the hospital. Suggested Technical Considerations After craniotomy, the microneurosurgical training begins under magnification (×5 – ×10 – ×20) using a table-mounted training operation microscope. The following microneurosurgical instruments are available for each trainee: bipolar forceps, brain retractors, an arachnoid knife, several micro dissectors, a pair of microscissors, and a suction tube.

9.3

Example of a Two-Part Training Methodology

9.3.1 Part 1 Midline supracerebellar infratentorial approach: Trainees are instructed to work through a list of five surgical steps (see Fig. 9.1): . Opening the cisterna magna A B. Identifying and dissecting the bridging vein(s) connecting the superior surface of the cerebellum to the tentorium cerebelli C. Identifying and dissecting the quadrigeminal cistern’s arachnoid layer D. Dissection and resection of the Galenic venous complex superior to the pineal gland (not applicable intraoperatively, aiming toward exposing all the relations of the pineal gland) E. Identifying and resecting the pineal gland

9.3.2 Part 2 Unilateral occipital transtentorial approach: This part consists of four surgical steps (see Figs. 9.2 and 9.3): . Identifying the tentorium cerebelli A B. Identifying and mobilizing the Galenic venous complex gently C. Dissecting the quadrigeminal cistern’s arachnoid layer D. Identifying and resecting the pineal gland

126

S. S. Hoz et al.

a

b

d

e

c

Fig. 9.1  Microneurosurgical steps of the midline supracerebellar infratentorial approach in the nonliving sheep training model (five-step approach). (a) Opening of the cisterna magna. (b) Dissection of the bridging vein(s) connecting the superior surface of the cerebellum to the tentorium cerebelli. (c) Identification and dissection of the quadrigeminal cistern’s arachnoid layer. (d) Identification and dissection of the Galenic venous complex superior to the pineal gland. (e) Identification, dissection, and resection of the pineal gland. C cerebellum, T tentorium, CM cisterna magna, MO medulla oblongata, BV bridging veins, PL pulvinar of thalamus, QC quadrigeminal cistern, SC superior colliculus of the midbrain, R retractor, G Galenic venous complex (the formation of vein of Galen from internal cerebral veins) within the quadrigeminal cistern (© Courtesy of Samer S.  Hoz, Hoz Neurosurgery Lab, Department of neurosurgery, Neurosurgery Teaching Hospital, Baghdad, Iraq)

9.4

Learning Points

The base of the pineal gland is the posterior wall of the third ventricle. The splenium of the corpus callosum lies above, and the thalamus surrounds the pineal gland on both sides. The pineal gland projects posteriorly and inferiorly into the quadrigeminal cistern. The deep cerebral veins, notably the internal cerebral veins, the veins of

9  Animal Based Surgical Training in Pineal Approaches

a

c

127

b

d

Fig. 9.2  Microneurosurgical steps of the unilateral occipital transtentorial approach in the nonliving sheep training model (four-step approach). (a) Identification of the tentorium cerebelli. (b) Identification and gentle dissection of the Galenic venous complex. (c) Identification and dissection of the quadrigeminal cistern’s arachnoid layer. (d) Identification, dissection, and resection of the pineal gland. O occipital lobe of cerebrum, T tentorium, G vein of Galen, F falx cerebri, PL pulvinar of thalamus, SC superior colliculus of the midbrain, P pineal gland, C cerebellum (© Courtesy of Samer S.  Hoz, Hoz Neurosurgery Lab, Department of neurosurgery, Neurosurgery Teaching Hospital, Baghdad, Iraq)

128

a

S. S. Hoz et al.

b

Fig. 9.3  Pineal region in the nonliving sheep training model. (a) Quadrigeminal cistern contents with Galenic venous system. (b) Pineal gland after removal of the Galenic venous system. ICV internal cerebral veins, PL pulvinar of thalamus, P pineal gland, SC superior colliculus of the midbrain, G vein of Galen, C cerebellum, T tentorium (© Courtesy of Samer S.  Hoz, Hoz Neurosurgery Lab, Department of neurosurgery, Neurosurgery Teaching Hospital, Baghdad, Iraq)

Rosenthal, the vein of Galen, and the straight sinus, are major obstacles to operations in this region, whereas the venous drainage of the pineal region must be preserved.

9.5

Pros of the Presented Model

There are several advantageous of the discussed model which renders it a valuable alternative to human cadavers and living animals. First, the nonliving sheep brain is readily available in most regions around the globe and thus convenient to use, and it is less prone for raising the ethical and regulatory concerns associated with human cadavers. It also does not require the specific facilities needed to maintain living animals. Second, the model is far more cost-effective than using human cadavers or living animals. Given the low costs and broad availability, residents in their early residency period have the opportunity to improve their skills in dealing with microneurosurgical instruments under the microscope while handling fresh organic specimens, simulating real operation conditions. Importantly, the anatomy of the sheep pineal region and its neurovascular relations are very similar to the one found in humans, particularly in infants. And even though a human cadaver would be even more superior for training purpose, feedback of participating residents in established training models was positive in a way that dismissed size and structural differences between the sheep and human brain as negatively affecting the educational value of the model [23–26].

9  Animal Based Surgical Training in Pineal Approaches

9.6

129

Cons of the Presented Model

One of the limitations of the presented model is the lack of active bleeding, which is present in living animal or simulation models. However, the aim of this module is not to deal with difficult hemostasis scenarios but rather offer training in arachnoid dissection and get full orientation and comprehension of the surgical anatomy, rendering this limitation of minor concern. Nevertheless, transferring the learned content into real-life practice is only valid when this important limitation is taken in consideration. Another issue, in spite of the generally low medical risk of contracting animal diseases such as bovine spongiform encephalopathy, proper precautions must be taken when using this model. It is recommended that the specimen be provided from a known source, optimally from animals under veterinary control. Understandably, surgical instruments used in training must not be used on human subjects afterward, and all possible sterilization measures should be considered [27–29].

9.7

Summary

The nonliving animal head model greatly simulates the standard neurosurgical procedures, and thus it is a useful, cost effective, and an easily applicable tool for developing and refining neurosurgical skills. It is an invaluable source for handling of neurosurgical equipment while experiencing properties of the cerebral brain texture and its haptic perception, and there are many neurosurgical approaches and procedures that can be simulated using this model. The simulation model for both the midline supracerebellar infratentorial and the unilateral occipital transtentorial approach to the pineal region is effective in providing neurosurgery residents with basic anatomical skills and microneurosurgical techniques for the access to the pineal region. The model based on fresh cadaveric sheep cranium is broadly available at low costs and is easy to prepare and reproduce. Active measures for further development and refinement of nonliving animal-based models and programs are warranted for optimized residency outcome.

References 1. Yaşargil MG.  From the microsurgical laboratory to the operating theatre. Acta Neurochir. 2005;147(5):465–8. 2. Dandy WE.  An operation for the removal of pineal tumors. Surg Gynecol Obstet. 1921;33:113–9. 3. Egermann M, Gerhardt C, Barth A, Maestroni GJ, Schneider E, Alini M. Pinealectomy affects bone mineral density and structure-an experimental study in sheep. BMC Musculoskelet Disord. 2011;12(1):271.

130

S. S. Hoz et al.

4. Tricoire H, Malpaux B, Møller M.  Cellular lining of the sheep pineal recess studied by light-, transmission-, and scanning electron microscopy: morphologic indications for a direct secretion of melatonin from the pineal gland to the cerebrospinal fluid. J Comp Neurol. 2003;456(1):39–47. 5. Güney M, Ayranci E, Kaplan S. Development and histology of the pineal gland in animals. Step by step experimental pinealectomy techniques in animals for researchers. New  York: Nova Science Publishers; 2013. p. 33–52. 6. Dempsey RJ, Hopkins J, Bittman EL, Kindt GW. Total pinealectomy by an occipital parasagittal approach in sheep. Surg Neurol. 1982;18(5):377–80. 7. Poppen JL. The right occipital approach to a pinealoma. J Neurosurg. 1966;25(6):706–10. 8. Menovsky T. A human skull cast model for training of intracranial microneurosurgical skills. Microsurgery. 2000;20(7):311–3. 9. Stienen MN, Netuka D, Demetriades AK, Ringel F, Gautschi OP, Gempt J, Kuhlen D, Schaller K. Residency program trainee-satisfaction correlate with results of the European board examination in neurosurgery. Acta Neurochir. 2016;158(10):1823–30. 10. Stienen MN, Netuka D, Demetriades AK, Ringel F, Gautschi OP, Gempt J, Kuhlen D, Schaller K. Working time of neurosurgical residents in Europe—results of a multinational survey. Acta Neurochir. 2016;158(1):17–25. 11. Suri A, Patra DP, Meena RK. Simulation in neurosurgery: past, present, and future. Neurol India. 2016;64(3):387. 12. Rehder R, Abd-El-Barr M, Hooten K, Weinstock P, Madsen JR, Cohen AR. The role of simulation in neurosurgery. Childs Nerv Syst. 2016;32(1):43–54. 13. Kirkman MA, Ahmed M, Albert AF, Wilson MH, Nandi D, Sevdalis N. The use of simulation in neurosurgical education and training: a systematic review. J Neurosurg. 2014;121(2):228–46. 14. Stienen MN, Schaller K, Cock H, Lisnic V, Regli L, Thomson S. eLearning resources to supplement postgraduate neurosurgery training. Acta Neurochir. 2017;159(2):325–37. 15. Roitberg B, Banerjee P, Luciano C, Matulyauskas M, Rizzi S, Kania P, Gasco J. Sensory and motor skill testing in neurosurgery applicants: a pilot study using a virtual reality haptic neurosurgical simulator. Neurosurgery. 2013;73(suppl_1):S116–21. 16. Hayashi S, Naito M, Kawata S, Qu N, Hatayama N, Hirai S, Itoh M. History and future of human cadaver preservation for surgical training: from formalin to saturated salt solution method. Anat Sci Int. 2016;91(1):1–7. 17. Stein BM.  The supracerebellar infratentorial approach to pineal lesions. J Neurosurg. 1971;35(2):197–202. 18. Hicdonmez T, et al. Posterior fossa approach: microneurosurgical training model in cadaveric sheep. Turk Neurosurg. 2006;16(3):111–4. 19. Hicdonmez T, Hamamcioglu MK, Tiryaki M, Cukur Z, Cobanoglu S.  Microneurosurgical training model in fresh cadaveric cow brain: a laboratory study simulating the approach to the circle of Willis. Surg Neurol. 2006;66(1):100–4. 20. Regelsberger J, Heese O, Horn P, Kirsch M, Eicker S, Sabel M, Westphal M. Training microneurosurgery–four years experiences with an in vivo model. Central Eur Neurosurg Zentralblatt für Neurochirurgie. 2011;72(04):192–5. 21. Aurich LA, Silva Junior LF, Monteiro FM, Ottoni AN, Jung GS, Ramina R. Microsurgical training model with nonliving swine head. Alternative for neurosurgical education. Acta Cir Bras. 2014;29(6):405–9. 22. Silva LF, Aurich L, Monteiro F, Zambon L, Nogueira G, Ramina R. Microsurgical and endoscopic training model with nonliving swine head: new alternative for skull base education. J Neurolog Surg Part B. 2014;75(S01):A190. 23. Sindou M. Practical handbook of neurosurgery, vol. 2. 1st ed. Vienna: Springer; 2009. p. 286. 24. Carey JN, Minneti M, Leland HA, Demetriades D, Talving P. Perfused fresh cadavers: method for application to surgical simulation. Am J Surg. 2015;210(1):179–87. 25. Greenberg MS, Greenberg MS.  Handbook of neurosurgery. 8th ed. Tampa: Greenberg Graphics; 2016. p. 663.

9  Animal Based Surgical Training in Pineal Approaches

131

26. Reiter RJ.  The mammalian pineal gland: structure and function. Am J Anat. 1981;162(4):287–313. 27. Yildiz D, Gultiken M, Bolat D. Arterial supply of the pineal gland of Akkaraman sheep. Acta Vet Hung. 2004;52(1):1–6. 28. Grist EP. Transmissible spongiform encephalopathy risk assessment: the UK experience. Risk Anal Int J. 2005;25(3):519–32. 29. Turan Suslu H, Ceylan D, Tatarlı N, Hıcdonmez T, Seker A, Bahrı Y, Kılıc T. Laboratory training in the retrosigmoid approach using cadaveric silicone injected cow brain. Br J Neurosurg. 2013;27(6):812–4.

Evolutionary Retrace of the Third Eye

10

Mohammed Maan Al-Salihi

In several vertebrates, the pineal gland functions as a photoreceptive neuroendocrine organ. Morphological and functional parallels between the pineal and retinal photoreceptor cells show their close evolutionary connection, and hence the comparative studies on the pineal gland and the retina are the keys to decrypting the evolutionary traces of the vertebrate photoreceptive structures. The determinations toward clarifying the molecular composition intrinsic to the pineal gland, back to back with those to the retina, should lead to an inclusive understanding of the evolutionary past of the vertebrate photoreceptive structures. The major characteristic of the pineal gland is the ability to role as a melatonin manufacturer that controls on a 24 h agenda, reflecting the exceptional synthetic capabilities of the pinealocyte. Melatonin synthesis is classically raised at night and assists to afford the organism with a signal of night-time. Melatonin levels can be observed as hands of the clock. Matters relating to the evolutionary events leading up to the emergence of this system have not received significant care. As more understanding has developed about the pinealocyte and the relationship it has to retinal photoreceptors, it has become possible to produce a reasonable hypothesis to clarify how the pineal gland and the melatonin rhythm evolved. The pineal gland which controls sleeping and waking cycles appears to have evolved as an indirect way to improve vision, by keeping toxic substance away from the eye; in numerous vertebrates, the pineal gland works as a photoreceptive neuroendocrine organ. Morphological and functional similarities between the pineal gland and retinal photoreceptor cells show their close relationship from evolutionary standpoint; hence the comparative revisions on the pineal gland and the retina are the way to interpreting the evolutionary traces of the vertebrate photoreceptive organs. The efforts toward explaining the molecular arrangement intrinsic to the pineal gland, consecutive with those to the retina, would lead to a wide-ranging M. M. Al-Salihi (*) College of Medicine, University of Baghdad, Baghdad, Iraq © Springer Nature Switzerland AG 2020 S. S. Hoz et al. (eds.), Pineal Neurosurgery, https://doi.org/10.1007/978-3-030-53191-1_10

133

134

M. M. Al-Salihi

understanding of the evolution of the vertebrate photoreceptive constructions. Profuse evidences from several disciplines expose that several distinguishing features are common by the pinealocyte and retinal photoreceptor. This formula of proof raised hastily in the last quarter of the twentieth century [1]. Functional evidence from ablation studies gave indirect sustenance to recommend that the submammalian pineal gland sensed light. However, it was not until electrophysiological studies have showed that fish and anuran pinealocytes sense light that the photosensitive capacity of pinealocyte was recognized [2–4]. Afterward, direct effects of light on isolated avian and fish pineal glands and pinealocytes in culture were defined in studies of the melatonin pathway [5–11]. Equally important was the affirmation that the retina shared the crucial characteristic of the pineal gland—the capacity to make melatonin [12, 13]. Although melatonin synthesis in the retina is very little, as compared to the pineal gland, it is obvious that the genes encoding the two enzymes devoted to melatonin production—AANAT and HIOMT—are expressed in the retinas of several, albeit not all, vertebrates. Melatonin is supposed to improve photoadaptation by the retina. In many cases, melatonin is manufactured locally for this purpose; however, in cases where melatonin does not seem to be manufactured, including the monkey, human, and cow [14–18]. Pineal-derived melatonin could perform in place of locally created melatonin through high affinity melatonin receptors [19–21]. Anatomical evidence of the similarity of the submammalian pinealocyte and retinal photoreceptor became clear from structural studies that labeled the photoreceptor elements of pinealocytes and recognized the mutual structures that common with the vertebrate retinal photoreceptor, counting a highly folded membranous outer segment, a 9 + 0 cilium, and a polarized organization, with a distinct cell body and centrosome [22–25]. The anatomical resemblance of the pineal and retinal photoreceptor has also become obvious from studies of mammalian pinealocytes that display photoreceptor features [26]. The adult pineal gland, however, does not hold those characteristics, and it is not photosensitive. Genetic evidence of the resemblances of the pineal gland and retinal photoreceptor began to be distinguished primarily in the 1970s with the usage of antisera against proteins found in the retinal photoreceptors [27, 28]. Measurements of both protein and mRNA subsequently established that many genes which are mandatory for retinal photo-transduction proteins are very copious in the mammalian pineal gland, including S-antigen, phosducin (MEKA), interphotoreceptor retinoid binding protein, opsin kinase, and recoverin [29–42]. In mammals, opsin is not produced at significant levels, telling that the highly expressed photo-transduction genes function in G-protein-mediated transduction in the pinealocyte. It appears that opsin was replaced by other G-protein-regulated receptors, most remarkably adrenergic and VIP receptors. Examination of photosensitive pinealocytes of fish showed that pineal-specific formulae of opsin exist [43–46], signifying the fish pineal gland evolved to meet different selective pressures than those which directed retinal photoreceptor evolution. Photoreceptor effectiveness has been informed for anuran, avian, and mammalian pinealocytes [47–52]. Throughout growth, these cells have the capacity to grow improved photoreceptor characteristics in culture and in vivo

10  Evolutionary Retrace of the Third Eye

135

in response to particular agents and transplantation routines, exhibiting that at an early stage in development, destiny can be shifted from a pinealocyte to retinal photoreceptor phenotype. Developmental regulatory mechanisms are common by both the pinealocyte and retinal photoreceptor. Remarkable molecular evidence is now amassing which shows that the growth of both contains analogous transcription factor cascades and that promoters of genes encoding proteins devoted to photo-­ transduction and melatonin encompass a variation of a sequence described as the photoreceptor-conserved element [53–59]. If the expression of OTX2, a gene obligatory for normal retinal growth, is excluded in the mouse, the pineal gland does not develop [60]. Brain tumors of the type described as trilateral retinoblastoma are also a confirmation to the link between the pinealocyte and retinal photoreceptor. The trilateral retinoblastoma is a type of retinoblastoma in which a midline tumor grows in the pineal region of subjects with uni- or bilateral retinoblastomas [61–63]. Embryological investigations have also established that both the pineal gland and retina develop from adjacent regions of the neural plate [57, 64, 65]. Variations on a theme seem to be a valid way to describe the pinealocyte and retinal photoreceptor. Although it is clear that they have become specialized, with respect to their relative capacity to synthesize melatonin and detect light, the notion that they both evolved from a single photosensitive melatonin synthesizing cell seems noticeable. • Melatonin was at initial a type of cellular debris, a by-product formed in the cells of the eye when classically toxic materials were rendered harmless. • Roughly 500  million years ago, however, the ancestors of today’s animals became reliant on melatonin as a sign of night. • As the necessity for larger quantities of melatonin grew, the pineal gland evolved as a structure distinct from the eyes, to retain the poisonous materials and to produce melatonin away from the sensitive tissue of the eye. • For sight to be possible, a form of vitamin A (also called retinaldehyde) must chemically attribute itself to rhodopsin, a protein that originates in the cells that detect light in the retina (the photoreceptors). • When hit by light, the retinaldehyde-rhodopsin complex undergoes physical fluctuations that begin a series of chemical reactions. These reactions eventually produce an electrical signal that journeys into the brain, making vision conceivable. • This is a one-time occurrence for each retinal-rhodopsin complex. In the process, light also renders the retinaldehyde inactive and frees it from rhodopsin. • The free, inactive retinaldehyde is then recycled within the retina to an active form, so that it can again contribute in light recognition. However, there is a problem arising from the recycling process: • When retinaldehyde is not in complex with rhodopsin, it can combine with other substances known as arylalkylamines.

136

M. M. Al-Salihi

• One molecule of an arylalkylamine is able to combine with two molecules of retinaldehyde to produce a material known as a bis-retinal arylalkylamine. After that combination, the retinaldehyde molecule is no more beneficial in the detection of the light. Arylalkylamines are actually hazardous because they can harm many substances in the cell. Some arylalkylamines are produced naturally. Those include tyramine, tryptamine, phenylethylamine, and serotonin. In addition, other toxic arylalkylamines were also existing in the environment early in evolution. And here comes the role of aralkylamine N-acetyltransferase (AANAT) in this evolutionary story: • AANAT chemically modifies arylalkylamines to impede them from uniting to retinaldehyde. • AANAT modifies serotonin by altering it to a complex known as N-­acetylserotonin. However, N-acetylserotonin is also toxic to the retinal cells, even though less so than is serotonin. A second enzyme, hydroxyindole-O-methyltransferase (HIOMT), further transformed N-acetylserotonin, altering it into melatonin, which is comparatively benign to the eye. Several features of AANAT and of retinal biochemistry can assist as guides in trying to understand the benefit that AANAT served: • First, AANAT can generally acetylate arylalkylamines [66–70]. • Second, AANAT present at significant levels merely in photodetector-derived cells, the pinealocyte, and retinal photoreceptor [71]. • Third, the substrates of AANAT as amines can react with retinaldehyde, the vital chemical of the visual cycle via Schiff base formation [72]. The importance of retinaldehyde to photo-detection is that one molecule of 11-cis-retinaldehyde is converted to the inactive all-trans form when a photon is seized. The reaction of amines with retinaldehyde can theoretically lead to exhaustion of retinaldehyde and synthesis of cytotoxic bis-retinyl arylalkylamines [72]. Moreover, a related class of aromatic amines, the arylamines, is known to be retinotoxic and to act via Schiff base formation, which in turn short circuits the visual cycle and stops the accumulation of 11-cis-retinaldehyde [73–75]. AANAT would avert these effects of arylalkylamines because N-acetylation renders the amine inactive, averting additional reactions unless a deacetylating enzyme is present to regenerate the amine. Accordingly, AANAT can be considered as a detoxification agent, much as arylamine N-acetyltransferase is considered in the liver and other organs, where it deactivates arylamines by N-acetylation [76–81]. In addition to deactivating the amine, N-acetylation also neutralizes the charge on the molecule communicated by the amine, thereby easing the removal of the complex by increasing its solubility in the lipid membranes of the cell.

10  Evolutionary Retrace of the Third Eye

137

Melatonin formation is likely to have evolved in steps: • Including the addition of hydroxyindole-O-methyltransferase (HIOMT). Like AANAT, it also would aid in a detoxification function because O-methylation lumps further alterations of hydroxyl groups resulting in more reactive derivatives. • In addition, O-methylation upsurges the lipid solubility of aromatic groups because methoxy derivatives have superior solubility in cell membranes. • In the early stages of evolution of melatonin formation, serotonin may not have been copious. Accordingly, AANAT and HIOMT may have served in a general role in detoxification, rather than being devoted to melatonin formation. However, the profusion of serotonin would upsurge as serotonin evolved into a beneficial transmitter. Regular rhythmic fluctuations in melatonin manufacture could have evolved from a pressure to improve photo-detection nightly: augmented detoxification of aromatic amines at dark could improve the available 11-cisretinaldehyde. Improved photo-detection would deliver a viable advantage to creatures at this stage in evolution, when life was evolving in an aqueous environment, which was most likely been dim and murky. With the challenge of low light levels, especially nightly, any mechanism which amplifies photosensitivity would be appreciated and delivers a selective competitive benefit. The amplified capacity to sense light in the dark primordial environment would give the ancestral vertebrate greater capacity to sense and avoid predators, navigate, and seek and capture nutrients in less populated darker niches. Melatonin signaling may have resulted from the broad activation of receptors that had evolved to sense other compounds. Melatonin was uncommon because it was providing a time signal, which would be of importance in synchronizing the organism with the 24  h photic environment. The everyday rhythm in melatonin may have synchronized all physiological functions. In the ancestor of today’s higher creatures, the alteration of serotonin to melatonin augmented at night, as a method to make vision more sensitive to low light circumstances. The alteration prevented serotonin from attaching to retinaldehyde at night, when it was wanted to sense low light levels, so that these ancestral animals could function fine under hazy light. Progressively, the early organism distinguished the increase in melatonin as a signal of dark and became reliant on it. This signal was used to synchronize their day-night cycles. For this signal to be dependable, the organism required a stable supply of serotonin in those cells. The necessity for higher levels of serotonin opposed with the need for better light sensing because serotonin exhausted retinaldehyde. This battle was resolved by the evolution of a second photoreceptor cell, one that possessed melatonin production capacity. The evolution of the second photoreceptor cell permitted the original photoreceptor cell to attain superior levels of sensitivity to light because it was not devoted to making high levels of melatonin. Eventually, the melatonin-making photoreceptors produced the pineal gland.

138

M. M. Al-Salihi

To upsurge both sets of procedures, melatonin formation and photo-detection evolution put them into discrete cells. One cell devoted to light detection, while the other toward melatonin synthesis. The photoreceptor cells of the retina strongly resemble the cells of the pineal gland and that the pineal cells of sub-mammals (such as fish, frogs and birds) sense light. In addition, melatonin’s origin in the ancestral photoreceptor cell is specified by the capacity of the retinas of mice, fish, frogs, and birds to produce low quantities of melatonin. As humans and other primates evolved, melatonin production was lost in the retina and became restricted to the pineal gland. Although melatonin is no longer produced in the primate retina, there’s still a suspicion that AANAT plays a role in shielding the human retina. Arylalkylamines (tryptamine, phenylethylamine, and tyramine) are likely to be formed in cells of the retina, and AANAT may serve to convert them to less injurious forms. Accordingly, AANAT may have two functions in the retina; it would have a detoxification role whereas in the pineal gland it would have a role in melatonin formation. It’s possible that low levels of AANAT might lead to the deterioration of the retina seen in macular degeneration; and perhaps it might be possible to prevent this disease by increasing AANAT levels.

References 1. Korf HW, Oksche A, Ekström P, van Veen T, Zigler JS, Gery I, Stein P, Klein DC. S-antigen immunocytochemistry. Pineal and retinal relationships. Orlando: Academic Press; 1986. p. 343–55. 2. Dodt E. Photosensitivity of the pineal organ in the teleost, Salmo irideus (gibbons). Cell Mol Life Sci. 1963;19(12):642–3. 3. Morita Y, Dodt E. Early receptor potential from the pineal photoreceptor. Pflügers Arch Eur J Physiol. 1975;354(3):273–80. 4. Dodt E, Meissl H.  The pineal and parietal organs of lower vertebrates. Cell Mol Life Sci. 1982;38(9):996–1000. 5. Rosner JM, de Pérez Bedés GD, Cardinali DP. Direct effect of light on duck pineal explants. Life Sci. 1971;10(18):1065–9. 6. Binkley SA, Riebman JB, Reilly KB. The pineal gland: a biological clock in vitro. Science. 1978;202(4373):1198–20. 7. Gern WA, Ralph CL. Melatonin synthesis by the retina. Science. 1979;204(4389):183–4. 8. Wainwright SD, Wainwright LK.  Chick pineal serotonin acetyltransferase: a diurnal cycle maintained in vitro and its regulation by light. Can J Biochem. 1979;57(6):700–9. 9. Hamm HE, Takahashi JS, Menaker M. Light-induced decrease of serotonin N-acetyltransferase activity and melatonin in the chicken pineal gland and retina. Brain Res. 1983;266(2):287–93. 10. Zatz M. Relationship between light, calcium influx and cAMP in the acute regulation of melatonin production by cultured chick pineal cells. Brain Res. 1989;477(1):14–8. 11. Falcon J, Marmillon JB, Claustrat B, Collin JP. Regulation of melatonin secretion in a photoreceptive pineal organ: an in vitro study in the pike. J Neurosci. 1989;9(6):1943–50. 12. Cahill GM, Grace MS, Besharse JC.  Rhythmic regulation of retinal melatonin: metabolic pathways, neurochemical mechanisms, and the ocular circadian clock. Cell Mol Neurobiol. 1991;11(5):529–60. 13. Iuvone PM, Tosini G, Pozdeyev N, Haque R, Klein DC, Chaurasia SS. Circadian clocks, clock networks, arylalkylamine N-acetyltransferase, and melatonin in the retina. Prog Retin Eye Res. 2005;24(4):433–56.

10  Evolutionary Retrace of the Third Eye

139

14. Wiechmann AF.  Localization of hydroxyindole-O-methyltransferase in the retina: a re-­ evaluation. Exp Eye Res. 1993;57(3):379. 15. Rodriguez IR, Mazuruk K, Schoen TJ, Chader GJ.  Structural analysis of the human hydroxyindole-O-methyltransferase gene. Presence of two distinct promoters. J Biol Chem. 1994;269(50):31969–77. 16. Bernard M, Donohue SJ, Klein DC.  Human hydroxyindole-O-methyltransferase in pineal gland, retina and Y79 retinoblastoma cells. Brain Res. 1995;696(1):37–48. 17. Craft CM, Murage J, Brown B, Zhan-Poe X. Bovine arylalkylamine N-acetyltransferease activity correlated with mRNA expression in pineal and retina. Mol Brain Res. 1999;65(1):44–51. 18. Coon SL, Mazuruk K, Bernard M, Roseboom PH, Klein DC, Rodriguez IR.  The human Serotonin N-Acetyltransferase (EC 2.3. 1.87) gene (AANAT): structure, chromosomal localization, and tissue expression. Genomics. 1996;34(1):76–84. 19. Reppert SM. Melatonin receptors: molecular biology of a new family of G protein-coupled receptors. J Biol Rhythm. 1997;12(6):528–31. 20. Barrett P, Conway S, Morgan PJ. Digging deep–structure–function relationships in the melatonin receptor family. J Pineal Res. 2003;35(4):221–30. 21. Dubocovich ML, Rivera-Bermudez MA, Gerdin MJ, Masana MI. Molecular pharmacology, regulation and function of mammalian melatonin receptors. Front Biosci. 2003;8:d1093–108. 22. Eakin RM. The third eye. Ther Ber. 23. Collin JP, Oksche A.  Structural and functional relationships in the nonmammalian pineal gland. Pineal Gland. 1981;1:27–67. 24. Ekström P, Meissl H. Evolution of photosensory pineal organs in new light: the fate of neuroendocrine photoreceptors. Philos Trans R Soc London B. 2003;358(1438):1679–700. 25. Klein DC. The 2004 Aschoff/Pittendrigh lecture: theory of the origin of the pineal gland—a tale of conflict and resolution. J Biol Rhythm. 2004;19(4):264–79. 26. Zimmerman BL, Tso MO. Morphologic evidence of photoreceptor differentiation of pinealocytes in the neonatal rat. J Cell Biol. 1975;66(1):60–75. 27. Kalsow CM, Wacker WB.  Pineal reactivity of anti-retina sera. Invest Ophthalmol Vis Sci. 1977;16(2):181–4. 28. Kalsow CM, Wacker WB. Pineal gland involvement in retina-induced experimental allergic uveitis. Invest Ophthalmol Vis Sci. 1978;17(8):774–83. 29. Somers RL, Klein DC. Rhodopsin kinase activity in the mammalian pineal gland and other tissues. Science. 1984;226:182–5. 30. Korf HW, Møller M, Gery I, Zigler JS, Klein DC. Immunocytochemical demonstration of retinal S-antigen in the pineal organ of four mammalian species. Cell Tissue Res. 1985;239(1):81–5. 31. Korf HW, Korl B, Schachenmayr W, Chader GJ, Wiggert B.  Immunocytochemical demonstration of interphotoreceptor retinoid-binding protein in cerebellar medulloblastoma. Acta Neuropathol. 1992;83(5):482–7. 32. Korf HW, White BH, Schaad NC, Klein DC. Recoverin in pineal organs and retinae of various vertebrate species including man. Brain Res. 1992;595(1):57–66. 33. Mirshahi M, Boucheix C, Collenot G, Thillaye B, Faure JP. Retinal S-antigen epitopes in vertebrate and invertebrate photoreceptors. Invest Ophthalmol Vis Sci. 1985;26(7):1016–21. 34. Donoso LA, Merryman CF, Edelberg KE, Naids R, Kalsow C. S-antigen in the developing retina and pineal gland: a monoclonal antibody study. Invest Ophthalmol Vis Sci. 1985;26(4):561–7. 35. Van Veen T, Katial A, Shinohara T, Barrett DJ, Wiggert B, Chader GJ, Nickerson JM. Retinal photoreceptor neurons and pinealocytes accumulate mRNA for interphotoreceptor retinoid-­ binding protein (IRBP). FEBS Lett. 1986;208(1):133–7. 36. Van Veen T, Ostholm TH, Gierschik P, Spiegel A, Somers R, Korf HW, Klein DC.  Alpha-­ Transducin immunoreactivity in retinae and sensory pineal organs of adult vertebrates. Proc Natl Acad Sci. 1986;83(4):912–6. 37. Van Veen T, Elofsson R, Hartwig HG, Gery I, Mochizuki M, Cena V, Klein DC.  Retinal S-antigen: immunocytochemical and immunochemical studies on distribution in animal photoreceptors and pineal organs. Exp Biol. 1986;45(1):15.

140

M. M. Al-Salihi

38. Rodrigues MM, Hackett J, Gaskins R, Wiggert B, Lee L, Redmond M, Chader GJ.  Interphotoreceptor retinoid-binding protein in retinal rod cells and pineal gland. Invest Ophthalmol Vis Sci. 1986;27(5):844–50. 39. Reig JA, Yu L, Klein DC. Pineal transduction. Adrenergic—cyclic AMP-dependent phosphorylation of cytoplasmic 33-kDa protein (MEKA) which binds beta gamma-complex of transducin. J Biol Chem. 1990;265(10):5816–24. 40. Schaad NC, Shinohara T, Abe T, Klein DC. Photoneural control of the synthesis and phosphorylation of pineal MEKA (phosducin). Endocrinology. 1991;129(6):3289–98. 41. Babila T, Schaad NC, Simonds WF, Shinohara T, Klein DC. Development of MEKA (phosducin), Gβ, Gγ and S-antigen in the rat pineal gland and retina. Brain Res. 1992;585(1):141–8. 42. Blackshaw S, Snyder SH. Developmental expression pattern of phototransduction components in mammalian pineal implies a light-sensing function. J Neurosci. 1997;17(21):8074–82. 43. Okano T, Yoshizawa T, Fukada Y.  Pinopsin is a chicken pineal photoreceptive molecule. Nature. 1994;372(6501):94–7. 44. Max M, McKinnon PJ, Seidenman KJ, Barrett RK, Applebury ML, Takahashi JS, Margolskee RF. Pineal opsin: a nonvisual opsin expressed in chick pineal. Science. 1995;267(5203):1502–6. 45. Mano H, Kojima D, Fukada Y. Exo-rhodopsin: a novel rhodopsin expressed in the zebrafish pineal gland. Mol Brain Res. 1999;73(1):110–8. 46. Kojima D, Fukada Y. Non-visual photoreception by a variety of vertebrate opsins. Novartis Found Symp. 1999;224:265–82. 47. Araki M. Developmental potency of cultured pineal cells: an approach to pineal developmental biology. Microsc Res Tech. 2001;53(1):33–42. 48. Araki M, Nonaka T, Watanabe K, Tokunaga F.  Phenotypic expression of photoreceptor and endocrine cell properties by cultured pineal cells of the newborn rat. Cell Differ Dev. 1988;25(2):155–63. 49. Araki M, Kodama R, Eguchi G, Yasujima M, Orii H, Watanabe K. Retinal differentiation from multipotential pineal cells of the embryonic quail. Neurosci Res. 1993;18(1):63–72. 50. Tosini G, Doyle S, Geusz M, Menaker M. Induction of photosensitivity in neonatal rat pineal gland. Proc Natl Acad Sci. 2000;97(21):11540–4. 51. Shimauchi Y, Yahata T, Matsubara S, Araki M. Role of tissue interaction between pineal primordium and neighboring tissues in avian pineal morphogenesis studied by intraocular transplantation. Dev Genes Evol. 2002;212(7):319–29. 52. Jangir OP, Suthar P, Shekhawat DV, Acbarya P, Swami KK, Sharma M. The “Third Eye”—A new concept of trans-differentiation of pineal gland into median eye in amphibian tadpoles of Bufo melanostictus. 53. Chen S, Wang QL, Nie Z, Sun H, Lennon G, Copeland NG, Gilbert DJ, Jenkins NA, Zack DJ. Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes. Neuron. 1997;19(5):1017–30. 54. Furukawa T, Morrow EM, Li T, Davis FC, Cepko CL. Retinopathy and attenuated circadian entrainment in Crx-deficient mice. Nat Genet. 1999;23(4):466–70. 55. Gamse JT, Shen YC, Thisse C, Thisse B, Raymond PA, Halpern ME, Liang JO. Otx5 regulates genes that show circadian expression in the zebrafish pineal complex. Nat Genet. 2002;30:1. 56. Bernard M, Dinet V, Voisin P.  Transcriptional regulation of the chicken hydroxyindole-­ O-­ methyltransferase gene by the cone–rod homeobox-containing protein. J Neurochem. 2001;79(2):248–57. 57. Ekström P, Meissl H. Evolution of photosensory pineal organs in new light: the fate of neuroendocrine photoreceptors. Philos Trans R Soc London B. 2003;358(1438):1679–700. 58. Appelbaum L, Toyama R, Dawid IB, Klein DC, Baler R, Gothilf Y. Zebrafish serotonin-N-­ acetyltransferase-­2 gene regulation: pineal-restrictive downstream module contains a functional E-box and three photoreceptor conserved elements. Mol Endocrinol. 2004;18(5):1210–21. 59. Appelbaum L, Anzulovich A, Baler R, Gothilf Y.  Homeobox-clock protein interaction in Zebrafish a shared mechanism for pineal-specific and circadian gene expression. J Biol Chem. 2005;280(12):11544–51.

10  Evolutionary Retrace of the Third Eye

141

60. Nishida A, Furukawa A, Koike C, Tano Y, Aizawa S, Matsuo I, Furukawa T.  Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development. Nat Neurosci. 2003;6(12):1255–63. 61. Jakobiec FA, Tso MO, Zimmerman LE, Danis P. Retinoblastoma and intracranial malignancy. Cancer. 1977;39(5):2048–58. 62. Bader J, Miller R, Meadows A, Zimmerman L, Champion LA, Voute PA. Trilateral retinoblastoma. Lancet. 1980;316(8194):582–3. 63. Mouratova T. Trilateral retinoblastoma: A. Bull Soc Belge Ophtalmol. 2005;297:25–35. 64. Calvo J, Boya J.  Embryonic development of the rat pineal gland. Anat Rec. 1981;200(4):491–500. 65. Tamminga CA. Images in neuroscience: brain development, I: the neural plate. Am J Psychiatry. 1998;155(3):324. 66. Voisin P, Namboodiri MA, Klein DC.  Arylamine N-acetyltransferase and arylalkylamine N-acetyltransferase in the mammalian pineal gland. J Biol Chem. 1984;259(17):10913–8. 67. Coon SL, Roseboom PH, Baler R, Weller JL, Namboodiri MA, Koonin EV, Klein DC. Pineal serotonin N-acetyltransferase: expression cloning and molecular analysis. Science. 1995;270(5242):1681–3. 68. Ferry G, Loynel A, Kucharczyk N, Bertin S, Rodriguez M, Delagrange P, Galizzi JP, Jacoby E, Volland JP, Lesieur D, Renard P.  Substrate specificity and inhibition studies of human Serotonin N-Acetyltransferase. J Biol Chem. 2000;275(12):8794–805. 69. Ferry G, Ubeaud C, Dauly C, Mozo J, Guillard S, Berger S, Jimenez S, Scoul C, Leclerc G, Yous S, Delagrange P. Purification of the recombinant human serotonin N-acetyltransferase (EC 2.3. 1.87): further characterization of and comparison with AANAT from other species. Protein Expr Purif. 2004;38(1):84–98. 70. Klein DC, Coon SL. The melatonin rhythm enzyme in the retina: a detoxification role. Ann Rev Pharmacol Tox (in press). 2006. 71. Klein DC, Coon SL, Roseboom PH, Weller JL, Bernard M, Gastel JA, Zatz M, Iuvone M, Rodriguez IR, Bégay V, Falcon J.  The melatonin rhythm-generating enzyme: molecular regulation of serotonin N-acetyltransferase in the pineal gland. Recent Prog Horm Res. 1997;52:307–58. 72. Klein DC. The 2004 Aschoff/Pittendrigh lecture: theory of the origin of the pineal gland—a tale of conflict and resolution. J Biol Rhythm. 2004;19(4):264–79. 73. Goodwin LG, Richards WH, Udall V.  The toxicity of diaminodiphenoxyalkanes. Br J Pharmacol. 1957;12(4):468–74. 74. Bernstein PS, Rando RR.  The specific inhibition of 11-cis-retinyl palmitate formation in the frog eye by diaminophenoxypentane, an inhibitor of rhodopsin regeneration. Vis Res. 1985;25(6):741–8. 75. Bernstein PS, Lichtman JR, Rando RR. Short-circuiting the visual cycle with retinotoxic aromatic amines. Proc Natl Acad Sci. 1986;83(6):1632–5. 76. Hein DW, McQueen CA, Grant DM, Goodfellow GH, Kadlubar FF, Weber WW.  Pharmacogenetics of the arylamineN-acetyltransferases: a symposium in honor of Wendell W. Weber. Drug Metab Dispos. 2000;28(12):1425–32. 77. Hein DW. N-Acetyltransferase genetics and their role in predisposition to aromatic and heterocyclic amine-induced carcinogenesis. Toxicol Lett. 2000;112:349–56. 78. Kilbane AJ, Petroff TH, Weber WW. Kinetics of acetyl CoA: arylamine N-acetyltransferase from rapid and slow acetylator human liver. Drug Metab Dispos. 1991;19(2):503–7. 79. Weber WW. Acetylating, deacetylating and amino acid conjugating enzymes. In: Concepts in biochemical pharmacology. Berlin, Heidelberg: Springer; 1971. p. 564–83. 80. Weber WW. Acetylation of drugs. In: Metabolic conjugation and metabolic hydrolysis, vol. III. Amsterdam: Elsevier; 1973. p. 249–96. 81. Weber WW. The acetylator genes and drug response. Oxford: Oxford University Press; 1987.